The circadian clock assures that diurnal animals, like humans, are alert during the day and asleep at night. Unfortunately, night shift workers are required to work during the "wrong" phase of their circadian cycle, when they are the most inefficient, sleepy, often fall asleep, and are most prone to accidents. Subsequently, they try to sleep during the day, again during the "wrong" phase of their circadian cycle, which results in disrupted and shortened sleep. The chronic sleep deprivation exacerbates the problem of having to work at night when the circadian clock makes people the sleepiest. Sleeping pills can help workers sleep during the day, but this does not eliminate the nighttime sleepiness and performance decrements caused by the circadian clock. Stimulants like coffee and pharmacological drugs can help workers remain alert during the night shift, but can interfere with subsequent daytime sleep. Furthermore, there is potential for side- effects, dependence and abuse with most drugs. The best solution for night work is to phase-shift the circadian clock to align with the night work and day sleep schedule. This re--alignment (re-entrainment) will alleviate the physiological symptoms of night work because the period of sleepiness will now occur during the daytime sleep period and the period of alertness will occur during the night shift. We tested various combinations of interventions designed to phase delay circadian rhythms and thus produce re-alignment. Young subjects who were not real shift workers (median age = 22, n=67) participated in 5 consecutive simulated night shifts (23:00 to 07:00) in the lab. The various interventions included a fixed daytime dark period for sleep at home, bright light during the night shift, sunglasses for the commute home and melatonin at bedtime. The daytime dark period was from 8:30 to 15:30 after each night shift, which we think is a reasonable daytime sleep schedule for a real night shift worker. It started 1.5 hours after the end of the night shift, leaving ample time to commute home and get ready for bed. We covered the bedroom windows with thick black plastic to make the rooms very dark for sleeping during the day. Because the study was run in the summer (3 consecutive summers), we installed air conditioners for subjects that did not already have them. The fixed daytime dark period creates a shifted (phase delayed) light dark (LD) cycle that "tells" the circadian clock to phase shift, i.e., to entrain to the new LD cycle. We have previously shown that bright light can either facilitate or inhibit the desired phase shift depending on its timing. Bright light before the body temperature minimum (Tmin) facilitates phase delays, whereas bright light after the Tmin facilitates advances. In this study, we exposed subjects to a gradually moving (delaying) pattern of intermittent bright light (approximately 5000 lux, 20 min on, 40 min off, 4-5 light pulses/night) or kept them in ordinary room light (dim light, approximately 150 lux) during the night shifts. We tested intermittent bright light because in areal night work setting it may be difficult for workers to remain exposed 1:0 the light sources for an extended amount of time. We ended the series of bright light pulses at 5:00 during the first night shift because we estimated the average baseline Tmin would be at about 5:00, and thus the bright light would facilitate phase delays. We moved the pattern one hour later on each subsequent night shift in order to phase delay the rhythms as far as possible (to keep up with the gradually delaying Tmin). The bright light was produced by 3 light boxes set on the perimeter of a large, round table facing in toward the center of the table. Subjects sat in the openings in between the light boxes so that each subject faced a light box. The light boxes (Apollo Light Systems Inc., Drem, UT, 61.0 cm wide, 77.5 cm high, 12.1 cm deep) contained cool-white fluorescent lamps. Sunglasses with normal or very dark lenses (15 or 2% light transmission) were used to attenuate sunlight during the commute home, which we expected to occur after the Tmin and thus inhibit the desired phase delay. Melatonin ( 1.8 mg, sustained release) or placebo was taken immediately before each daytime sleep (8:30am), a time expected to facilitate phase delays. A sustained release preparation was used to enhance the soporific effect throughout the daytime sleep period. The study included 6 intervention groups (6 combinations of the interventions mentioned above), which differed in the type and number of interventions and therefore in the amount of effort that would be required if adopted by real night shift workers and their employers. The 6 groups were: 1) dark daytime period for sleep + normal sunglasses, 2) dark daytime period for sleep + dark sunglasses, 3) dark daytime period for sleep + and dark sunglasses + melatonin, 4) dark daytime period for sleep + normal sunglasses + bright light, 5) dark daytime period for sleep + dark sunglasses + bright light, and 6) dark daytime period for sleep + dark sunglasses + bright light + melatonin. The subjects who did not get bright light during the night shift remained in room light. The subjects who did not take melatonin before bed took placebo (double-blind). The dim light melatonin onset (DLMO) was our marker for the phase of the circadian clock, and was assessed before and after the night shifts (baseline and final). We estimated the Tmin as the DLMO + 7 hours. A reasonable goal for circadian adaptation to the night work and day sleep is to phase shift circadian rhythms so that the sleepiest part of the circadian cycle, the Tmin, falls within the daytime sleep episode. Therefore, subjects were categorized by their amount of re-entrainment (re-alignment) based on their final Tmin: not re-entrained (Tmin before the daytime dark/sleep period), partially re-entrained (Tmin during the first half of dark/sleep), or completely re-entrained (Tmin during the second half of dark/sleep). Computerized neurobehavioral batteries were completed during each night shift. Sleep logs were verified by wrist activity monitors and photosensors worn around the neck like a medallion. Subjects exhibited a wide range of baseline circadian phases, as would real night shift workers. We split the sample into earlier subjects (baseline Tmin <7:00, sunlight during the commute home fell after the Tmin and would thus inhibit the desired phase delay) and later subjects (baseline Tmin > 7:00). The later subjects were completely re-entrained regardless of intervention group, whereas the degree of re-entrainment for the earlier subjects was improved by some of the interventions. Most of the earlier subjects in group 1 did not entrain. When the earlier subjects were given bright light during the night shift (groups 4, 5 and 6) all but one achieved complete re-entrainment, and the phase delay shift for the rest was so large that darker sunglasses and melatonin could not increase its magnitude. With only room light during the night shift, darker sunglasses helped earlier subjects phase delay more than normal sunglasses (group 2 compared to group 1). However, the darker sunglasses contain welders' lenses and are not designed for driving. Melatonin did not confer a benefit either for phase delaying or for increasing sleep duration. Although subjects slept about 6.5 hours during the day, night shift sleepiness and performance did not improve unless there was circadian phase alignment (partial or complete re-entrainment). Subjects who re-entrained did significantly better than subjects who did not re-entrain on the Psychomotor Vigilance Task (PVT), the Digit Symbol Substitution Test (DSST), the Stanford Sleepiness Scale (SSS), the Karolinska Sleepiness Scale (KSS) and the Physical Exhaustion and Tiredness Visual Analog Scales (V AS). There was no difference in these neurobehavioral measures between those who were partially and completely re-entrained, perhaps because our subjects were so young and thus "phase tolerant." This study showed that circadian adaptation to fixed night shifts is possible. Subjects with very late circadian rhythms need only maintain a fixed, dark, daytime period for sleep and wear normal sunglasses during the commute home. For subjects who start the night shift with earlier circadian rhythms, we recommend the combination of intermittent bright light during the night shift, sunglasses (as dark as possible) during the commute home, and a regular, early daytime dark/sleep period for complete circadian adaptation to night shift work.