OBJECTIVES: To examine the hypothesis that sedentary women have an increased risk of endometrial cancer compared to physically active women. METHODS: This is a population-based case-control study in the entire Swedish female population aged 50-74 years in 1994-1995. We obtained self-reported information on leisure-time physical activity during childhood, at ages 18-30, and recently from 709 incident case women with endometrial cancer and 3368 population controls. Occupational physical activity was estimated through record linkage to the Swedish census data from 1960, 1970, 1980, and 1990. Odds ratios (OR) and 95% confidence intervals (CI) were calculated for different activity levels by multivariate logistic regression, taking into account potential confounders. RESULTS: Comparing lowest to highest (reference) levels of physical exercise, we observed statistically significant associations with risk of endometrial cancer for leisure-time activity at age 18-30 years (multivariate OR = 1.4; 95% CI = 1.0-1.8; p for trend 0.01) and in recent years (multivariate OR = 1.3; 95% CI = 1.0-1.7; p for trend 0.01). We found similar associations comparing lowest to highest (reference) levels of occupational activity assessed at the censuses in 1980 (multivariate OR = 1.4; 95% CI = 1.0-1.9; p for trend 0.03) and 1990 (multivariate OR = 1.3; 95% CI = 0.9-1.9, p for trend 0.05), but a less consistent association with censuses in 1960 and 1970. The increased risk associated with low level of occupational physical activity was confined to women who were not obese and to women who were smokers. CONCLUSION: Our data, in conjunction with past epidemiological studies, indicate that both occupational and leisure-time physical activity may reduce the risk for postmenopausal endometrial cancer.