The chemopreventive properties of allyl sulfides on carcinogenesis may be related to the modulation of drug-metabolizing enzymes involved in carcinogen activation or detoxication. In order to investigate the effects of diallyl sulfide (DAS) and diallyl disulfide (DADS) on intestinal and hepatic drug-metabolizing enzymes, rats were fed a diet containing 0.2% of either allyl sulfide. The DADS enhanced intestinal epoxide hydrolase (EH) and cytochrome P-450 (P-450) 2B1/2 protein levels and the activities of pentoxy- and benzyl-oxyresorufin O-dealkylases, arylhydrocarbon hydroxylase, microsomal epoxide hydrolase, p-nitrophenol UDP-glucuronyl transferase and glutathione S-transferase, and decreased nitrosodimethylamine demethylase activity. In liver, DADS produced similar effects and, in addition, increased P-450 1A1/2 protein level and phenoxazone metabolizing activities (ethoxy- and methoxyresorufin O-dealkylases), p-hydroxybiphenyl UDP-glucuronyl transferase, and decreased P-450 2E1 level. The DAS enhanced only EH activity in the small intestine and induced P-450 2B1/2 and epoxide hydrolase protein levels. In liver, DAS produced similar effects as DADS. The different effects of DAS on intestinal drug-metabolizing enzymes, compared to liver, could be ascribed to less metabolism of this compound in small intestine. It is also suggested that DAS and DADS may not yield the same metabolites and therefore would have different effects on intestinal drug-metabolizing enzymes.