It was proposed in 1980 that vitamin D and calcium could reduce the risk of colon cancer. This assertion was based on the decreasing gradient of mortality rates from north to south, suggesting a mechanism related to a favorable influence of ultraviolet-induced vitamin D metabolites on metabolism of calcium. A 19-y prospective study of 1954 Chicago men found that a dietary intake of greater than 3.75 micrograms vitamin D/d was associated with a 50% reduction in the incidence of colorectal cancer, whereas an intake of greater than or equal to 1200 mg Ca/d was associated with a 75% reduction. Clinical and laboratory studies further support these findings. A nested case-control study based on serum drawn from a cohort of 25,620 individuals reported that moderately elevated concentrations of 25-hydroxyvitamin D, in the range 65-100 nmol/L, were associated with large reductions (P less than 0.05) in the incidence of colorectal cancer.