Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is the major pungent principle of hot peppers of the genus Capsicum. There have been numerous investigations to evaluate the effects of capsaicin on experimental carcinogenesis and mutagenesis, but the results are discordant. In the present study, we have assessed the tumor promoting potential of capsaicin using a two stage mouse skin carcinogenesis model. Repeated applications of capsaicin (10 mumol) onto the shaven backs of female ICR mice following a single-initiation dose of 7,12-dimethylbenz[alpha]anthracene did not cause any significant increase in papilloma formation and abnormal hyperplastic or inflammatory skin lesions, compared with the solvent control. Furthermore, the topical application of capsaicin did not induce the epidermal ornithine decarboxylase activity, suggesting that it lacks tumor-promotional activity. On the contrary, the compound ameliorated the mouse skin carcinogenesis when given simultaneously with the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate.