To investigate whether a high intake of calcium, vitamin D, or dairy products may protect against colon cancer, the authors analyzed data from a prospective cohort study of 35,216 Iowa women aged 55-69 years without a history of cancer who completed a dietary questionnaire in 1986. Through 1990, 212 incident cases of colon cancer were documented. Adjusted for age, intakes of calcium and vitamin D were significantly inversely associated with the risk of colon cancer. The relative risks for the highest quintile of intake as compared with the lowest were 0.52 (95% confidence interval (CI) 0.33-0.82) for calcium and 0.54 (95% CI 0.35-0.84) for vitamin D. After multivariate adjustment, the trends were no longer statistically significant and the relative risks for the highest versus the lowest quintiles of calcium and vitamin D intakes were attenuated: 0.68 (95% CI 0.41-1.11) for calcium and 0.73 (95% CI 0.45-1.18) for vitamin D. Although the multivariate-adjusted findings did not reach statistical significance at p less-than-or-equal-to 0.05, when considered in the context of the whole body of literature on this subject, they are consistent with a possible role for calcium or vitamin D in modestly reducing colon cancer risk.