The effects of low, adequate, and supplemental intake of calcium and vitamin D3 on 12-O-tetradecanoylphorbol-13-acetate (TPA) skin tumor promotion were examined. Administration of the experimental diets was started one week before the first TPA application to the 7,12-dimethylbenz[a]anthracene-initiated dorsal skin of female Sencar mice. Neither dietary calcium in a range from 0.15% to 2.0% of the diet as calcium carbonate nor vitamin D3 ranging from 200 to 4,000 IU/kg diet resulted in modulation of the skin papilloma response in terms of incidence, number per mouse, or size distribution of tumors. There were also no effects of the varied levels of calcium or vitamin D3 on mouse body weights, serum calcium, or TPA induction of epidermal ornithine decarboxylase activity. These results indicate that dietary administration of a wide range of doses of calcium or vitamin D does not alter the serum calcium levels and, therefore, does not appear capable of altering skin tumor promotion. These results are in contrast to reports that demonstrate antineoplastic activity for both calcium ion and active hormonal vitamin D, either in control of epidermal cell proliferation and/or differentiation or inhibition of carcinogenesis.