US commercial airline pilots, like all flight crew, are at increased risk for specific cancers, but the relation of these outcomes to specific air cabin exposures such as cosmic radiation and circadian disruption is unclear. Flight time is often used as a surrogate for exposure to cosmic radiation. Our objectives were to develop methods to estimate exposures to cosmic radiation and circadian disruption, and to describe workplace exposures for this group of pilots. Exposures were estimated between August 1963 and March 2003 for 83 pilots from a major US airline, based on over 500,000 individual flight segments as well as summary records from other sources. Pilots flew a median of 7,126 flight segments and 14,959 block hours over 27.8 years of flight experience. In the final study year, a median pilot incurred an estimated effective dose of 1.922 mSv (absorbed dose, 0.846 mGy) from cosmic radiation and crossed 362 time zones. A study pilot was possibly exposed to a moderate- or large-sized Solar Particle Event (SPE) a median of 6 times in their work history, or once every 3.7 years of work. An index of work during the standard sleep interval (SSI travel) also suggested potential chronic sleep disturbance in some pilots. For study airline flights, median segment radiation doses, time zones crossed, and SSI travel increased markedly since the 1990s. Dose metrics were moderately correlated with questionnaire-edited self-reported flight experience (Spearman r = 0.66 - 0.69). This detailed assessment of individual flight segments is likely to decrease exposure misclassification in flight crew health studies.