A historical cohort mortality study was conducted among 28,008 white male employees who had worked for at least 1 month in Oak Ridge, Tennessee, during World War II. The workers were employed at two plants that were producing enriched uranium and a research and development laboratory. Vital status was ascertained through 1980 for 98.1% of the cohort members and death certificates were obtained for 96.8% of the 11,671 decedents. A modified version of the traditional standardized mortality ratio (SMR) analysis was used to compare the cause-specific mortality experience of the World War II workers with the U.S. white male population. An SMR and a trend statistic were computed for each cause-of-death category for the 30-year interval from 1950 to 1980. The SMR for all causes was 1.11, and there was a significant upward trend of 0.74% per year. The excess mortality was primarily due to lung cancer and diseases of the respiratory system. Poisson regression methods were used to evaluate the influence of duration of employment, facility of employment, socioeconomic status, birth year, period of follow-up, and radiation exposure on cause-specific mortality. Maximum likelihood estimates of the parameters in a main-effects model were obtained to describe the joint effects of these six factors on cause-specific mortality of the World War II workers. We show that these multivariate regression techniques provide a useful extension of conventional SMR analysis and illustrate their effective use in a large occupational cohort study.