Vitamin D affects calcium metabolism and prevents proliferation of colon cells in vitro. In human beings the main circulating form of vitamin D is 25-hydroxyvitamin D; to regulate calcium homoeostasis, this form must be converted to 1alpha, 25-dihydroxyvitamin D by 1alpha-hydroxylation in the kidney with 25-hydroxyvitamin D-1alpha-hydroxylase. Cultured transformed colon cancer cells can convert 25-hydroxyvitamin D(3) to 1alpha,25-dihydroxyvitamin D(3). We identified messenger RNA (mRNA) for 25-hydroxyvitamin D-1alpha-hydroxylase in normal colon tissue and in malignant and adjacent normal colon tissue. These findings support the notion that vitamin D might have a role in cell growth regulation and cancer protection, and might be the explanation for why the risk of dying from colorectal cancer is highest in areas with the least amount of sunlight.