Excess weight near the time of diagnosis is a well-established risk factor for endometrial cancer; less is known about the influence of weight at earlier periods of a woman's life or weight gain in adulthood. In a case-control study in western New York State, interviews were conducted with 232 incident endometrial cancer cases, diagnosed between 1986 and 1991, and 631 community controls. Body mass index at 16 years of age and 20, 10, and 2 years before interview and changes in body mass index between these time periods were examined. While being relatively heavy at 16 years of age was associated with slightly increased risk [adjusted odds ratio (OR) = 1.28, 95% confidence interval (CI) = 0.84-1.96], large gains over the entire period from 16 years of age to 2 years ago (OR = 3.45, CI = 2.13-5.57) and high body mass index close to the time of diagnosis (OR = 3.21, CI = 2.01-5.15) were associated with greater risk. Differences in mean body mass index between cases and controls increased over time.