Because of previously reported hepatic abnormalities in burns, the activity of the hepatic drug metabolizing system was assessed in burned Sprague-Dawley rats. In 16% burned male rats, pentobarbital sleeping times were significantly prolonged from day 1 to day 24 ostburn, and trichloroethanol sleeping times were significantly prolonged from day 1 to day 10 postburn. The activity of p-nitroanisole O-demethylase was significantly depressed in male rats at 5, 10, and 17 days post-16% burn. In female rats, this enzyme was more depressed at 10 days post-16% burn than in male rats. A direct relationship was found between per cent burn and impairment of enzyme activity. The depression of drug metabolizing enzymes was inducible by phenobarbital pretreatment. Pretreatment with the immunosuppressive drug azathioprine prevented the enzyme depression at 5 days postburn, a result which possibley implicates a postburn hyperimmune response as the mechanism for the depressed enzyme levels.