Case-control studies of lifestyle factors have been inconclusive in the study of endometrial cancer, and prospective data are scarce. Our aim was to examine the associations of physical activity, weight and weight change, fruit, vegetable, and alcohol consumption, socio-economic status, parity and presence of diabetes mellitus with the risk of endometrial cancer in a cohort study. In 1967, 11,659 women in the Swedish Twin Registry, born 1886-1925, answered a 107-item questionnaire, including questions about diet, physical activity and other lifestyle factors. Complete follow-up through 1992 was attained through record linkage to the Swedish Cancer and Death Registers. The relative risks for endometrial cancer were estimated in proportional hazards models that adjusted confidence limits for correlated outcomes. We observed 133 incident cases of endometrial cancer in the cohort. There was no clear pattern of risk over strata of alcohol or fruit and vegetable intake, although the data suggest an increased risk with very low fruit and vegetable intake. Increasing physical activity markedly decreased the risk of endometrial cancer (p for trend F 0.01), independently of weight and parity; the risk in the highest quartile, relative to the sedentary category, was 0.2 (95% CI 0.3-0.8). As expected, higher weight in middle age increased the risk (p for trend F 0.01), as did higher weight in early adulthood. Contrary to previous findings, weight gain did not have an effect independent of weight at enrollment. We did not find a genetic component to endometrial cancer. Our results confirm that environmental factors are the most important, especially physical activity, parity, and weight in young and middle age.