Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is a principal pungent ingredient of hot red peppers. There are some controversies with regard to its inherent tumorigenicity and mutagenicity. The present work was undertaken to assess tumor initiating and promotional effects of capsaicin in a two-stage mouse skin carcinogenesis model. A single topical application of capsaicin (10 micromol) followed by twice-weekly applications of 12-O-tetradecanoylphorbol-13-acetate onto shaven backs of female ICR mice resulted in no significant increases in incidence and multiplicity of skin tumors, compared with the solvent-pretreated control animals. Repeated topical applications of capsaicin alone failed to promote 7,12-dimethylbenz[a]anthracene-initiated mouse skin tumorigenesis, but moderately inhibited the papilloma formation when given prior to each topical dose of phorbol ester.