Acceptable exposure limits for methylene-chloride (75092) (MC) were investigated. Twenty human volunteers were exposed to 50, 100, 250, and 500 parts per million (ppm) MC vapor for 1, 3, and 7.5 hours per day, 5 days per week for up to 6 weeks. At various times before and after exposure, the subjects underwent complete medical examinations, including determinations of urinary urobilinogen, alveolar MC and carbon-monoxide (CO), blood carboxyhemoglobin (COHb), neurological function, pulmonary function, blood biochemistry, and cognitive testing. Alveolar MC concentrations correlated with duration and degree of exposure. The persistence of alveolar MC was also correlated to degree of exposure. No accumulation of MC with repeated exposure was evident. Results of alveolar CO measurements were not reported. MC caused significant, dose related increases in blood COHb. COHb continued to increase for up to 2 hours after exposure. The biological half life was twice as long as that reported for COHb produced by exposure to CO. MC exposure did not affect the functional integrity of the airways, alveolar capillary gas exchange, or pulmonary ventilation. Increases in hemoglobin affinity for oxygen were associated with the increased COHb values. No significant MC related changes in neurologic function or cognitive ability were recorded. The authors conclude that the threshold limit value for MC should be set at 50ppm to avoid excessive COHb body burdens. Breath analysis for MC or its metabolite, CO, provides an excellent test for determining the magnitude of exposure, and can be used as a Biological Threshold Limit measurement for exposed workers.