The active form of vitamin D, 1alpha,25-dihydroxyvitamin D (1alpha,25(OH)2D), inhibits proliferation and induces the differentiation of prostate cells in culture, attenuates tumor growth in animal models, and decreases prostate specific antigen (PSA) levels in prostate cancer patients. The enzymes that are responsible for the activation of vitamin D to 1alpha,25(OH)2D include vitamin D-25-hydroxylase (25-OHase) and 25-hydroxyvitamin D-1alpha-hydroxylase (1alpha-OHase or CYP27BJ) and are present in cultured prostate cells. The demonstration that a differential expression of 1alpha-OHase between noncarcinogenic and carcinogenic prostate cells and the ability of epidermal growth factor (EGF) to up-regulate 1alpha-OHase promoter activity in the noncarcinogenic, not the carcinogenic prostate cells suggested that a dysregulation of 1alpha-OHase in cancer cells may lead to the aberrant growth of prostate cancer cells. Thus, the 1alpha-OHase gene is a tumor suppressor gene responsible for the normal regulation of prostate cell growth.