The effect of the potent synthetic protease inhibitor [N,N-dimethylcarbamoylmethyl 4-(4-guanidinobenzoyloxy)-phenylacetate] methanesulfate (FOY-305) on skin carcinogenesis in ddY mice was examined over a total observation period of 105 days. Administration of 0.1% FOY-305 in the diet suppressed the incidence of carcinomas induced by repeated local application of the carcinogen 3-methylcholanthrene (MCA) (P less than .05) in mouse skin and delayed the time of appearance of the skin tumors (P less than .001). There was no significant difference in the number of tumors per tumor-bearing mouse and the size of the tumors between mice treated with MCA and mice treated with MCA plus FOY-305.