No hepatotoxicity was demonstrated after 90 days in rats treated with two dose levels of disulfiram. A reversible inhibition of microsomal p-nitroanisole demethylase activity was found. In phenobarbital-treated rats disulfiram 100 mg/kg did not alter the induction response as indicated by the cytochrome P-450 content, but inhibited the p-nitroanisole activity to control levels. As no sign of histological liver damage was found, we conclude that the rare cases of disulfiram hepatotoxicity in man may be due to an allergic reaction.