Despite the special working environment and exposures of airline pilots, data on risk of death and cancer incidence in this occupational group are limited. The authors investigated a cohort of 2,740 Air Canada pilots who contributed 62,449 person-years of observation. All male pilots employed for at least 1 year on and since January 1, 1950, were studied. The cutoff date for outcome information was December 31, 1992. Standardized mortality ratio (SMR) and standardized incidence ratio (SIR) were used to compare mortality rates and cancer incidence rates of the cohort with the respective Canadian population rates. Ninety percent confidence intervals of the SMR and SIR were calculated. Statistically significant decreased mortality was observed for all causes (SMR = 0.63, 90% confidence interval (CI) 0.56-0.70), for all cancers (SMR = 0.61, 90% CI 0.48-0.76), and for all noncancer diseases (SMR = 0.53, 90% CI 0.45-0.62). Mortality from aircraft accidents was significantly raised (SMR = 26.57, 90% CI 19.3-35.9). Significantly decreased cancer incidence was observed for all cancers (SIR = 0.71, 90% CI 0.61-0.82), rectal cancer (SIR = 0.42, 90% CI 0.14-0.96), lung cancer (SIR = 0.28, 90% CI 0.16-0.46), and bladder cancer (SIR = 0.36, 90% CI 0.12-0.82). Prostate cancer (SIR = 1.87, 90% CI 1.38-2.49) and acute myeloid leukemia (SIR = 4.72, 90% CI 2.05-9.31) were significantly increased. The preferred relative risk model for radiation-induced nonchronic lymphoid leukemia (Beir V report) was applied to the cohort by using published estimates of in-flight radiation exposures. The estimated relative risk ranged from 1.001 to 1.06 and did not differ significantly from the observed SIR (SIR = 1.88, 90% CI 0.80-3.53). However, the incidence rate of acute myeloid leukemia was significantly increased. Monitoring of in-flight radiation exposure and long-term follow-up of civil aviation crew members is needed to further assess cancer incidence and leukemia risk in this special occupational group.