Prolonged topical treatment with protease inhibitors (PIs) both synthetic and of bacterial origin have been shown to prevent carcinogen initiated and croton oil or phorbol acetate promoted skin carcinogenesis in mice. However, no one has yet examined the possibility of a purified PI of plant origin to block skin carcinogenesis by sustained local treatment. We therefore studied this aspect using a purified PI from field bean (FBPI) in Swiss albino mice. Groups of 8-week-old mice were taken and treated differently. Group I mice were treated with 100 microliters of acetone alone, while mice of Group II were treated with a single high (150 micrograms) dose of 7,12-dimethylbenz[a]anthracene in acetone and 2 weeks later they were treated with a high concentration (125 micrograms) of croton oil thrice weekly. Mice of Groups III, IV and V were treated exactly as described for mice of Group II, but 4 h after croton oil treatment they were further treated with an aqueous solution of 1 mg, 2 mg of FBPI or 2 mg of heat-inactivated [corrected] FBPI, respectively. Treatment of all groups was continued until the mice were 25 weeks old, the appearance of tumors being recorded during the period. Our findings showed that treatment of carcinogen and croton oil exposed mice of Groups III and IV with two different doses of FBPI not only brought about appreciable delay in the appearance of tumors but also significant (P < 0.025-0.001) suppression of tumor incidence at nearly all times of promotion. Additionally, it lowered significantly (P < 0.01-0.001) the tumor multiplicity and the tumor appearance rate compared to mice of Groups II and V. These effects of FBPI appeared to be dose related. Lack of response with heat-inactivated FBPI indicated that these actions of FBPI were related to its PI activity. The study thus confirmed that topical treatment with a legume-derived PI can effectively suppress skin carcinogenesis.