We studied the ability of a soybean extract containing the Bowman-Birk protease inhibitor (BBI), referred to as BBI concentrate (BBIC), purified BBI (PBBI), and the chymotrypsin inhibitor from potatoes to suppress oral carcinogenesis in hamsters induced by 7,12-dimethyl-benz[a]anthracene (DMBA). Application of 1% solutions of BBIC and PBBI five times per week to DMBA-treated hamster cheek pouches were highly effective in suppressing oral carcinogenesis, whereas a 1% solution of the chymotrypsin inhibitor from potatoes did not lead to a significant suppression of carcinogenesis. BBIC and PBBI suppressed carcinogenesis at concentrations ranging from 1% to 0.01% and were equally effective when given as a 1% solution five times per week, three times per week, or once per week. A 1% solution of BBIC suppressed oral carcinogenesis when given at the following times during the assay period: 0-180, 0-90, 14-90, and 45-135 days. Thus, protease inhibitor treatment could be started as late as 45 days after the beginning of the carcinogen exposure and have an irreversible suppressive effect on the carcinogenic process.