In vivo and in vitro studies have suggested a protective role of calcium and vitamin D in the development of colorectal cancer. However, epidemiologic data have been inconclusive. The authors prospectively assessed intakes of calcium and vitamin D in relation to risk of colorectal cancer in a large, prospective, female cohort from the US Women's Health Study. In 1993, 39,876 women aged > or = 45 years and free of cardiovascular disease and cancer were enrolled in the study. During an average follow-up of 10 years, 223 of 36,976 women eligible for the present study developed colorectal cancer. Intakes of calcium and vitamin D from dietary sources and supplements were assessed with a baseline food frequency questionnaire. Cox proportional hazards regression was used to estimate relative risks and 95% confidence intervals. Intakes of total calcium and vitamin D were not associated with risk of colorectal cancer; multivariate relative risks comparing the highest with the lowest quintile were 1.20 (95% confidence interval: 0.79, 1.85; p for trend = 0.21) for total calcium and 1.34 (95% confidence interval: 0.84, 2.13; p for trend = 0.08) for total vitamin D. Intakes of both nutrients from specific types of sources, including diet and supplements, were also not significantly associated with colorectal cancer risk. Data provide little support for an association of calcium and vitamin D intake with colorectal cancer risk.