To further characterize the association of obesity and endometrial cancer, in particular with regard to the role of early-age obesity and adult weight gain, the authors assembled by computer linkage a population-based historical cohort of 30,266 women born between 1913 and 1932, for whom weight and height had been recorded in 1942-43 and 1972. Linkage of this cohort to the Hawaii Tumor Registry resulted in the Identification of 214 (mainly post-menopausal) Incident cases of endometrial cancer for 1972-1986. An average of 3.7 cancer-free controls were matched to each case on month and year of birth and ethnicity. A case-control analysis, conducted In each 5-year birth cohort, revealed no clear association of endometrial cancer with weight, height or body mass at ages 10 to 29 years. However, positive associations with adult body weight and gain in body mass since 1942 were observed for women diagnosed at age 60 or older. This association with obesity was strongest in women whose body mass was below the median in 1942 and equal to or above the median in 1972. No association with body size was detected in women diagnosed before age 60. Parity, age at first birth and socio-economic indicators for 1942 and 1972 did not confound the analysis. These findings suggest that obesity affects the late stages of endometrial carcinogenesis, and the possibility that one or more determinants of weight gain may be independently associated with endometrial cancer risk.