S-Adenosylmethionine (800 mg i.v. per day) was used to treat two brothers and a brother and sister from each of two kindreds with benign recurrent intrahepatic cholestasis. Symptoms, routine tests of liver function, concentrations of total bile acids, and the oral clearances of [11,12-2H]chenodeoxycholic acid and [24-13C]cholic acid were determined before and after treatment with S-adenosylmethionine. S-Adenosylmethionine did not ameliorate symptoms or biochemical parameters of cholestasis but reduced bile acid clearances in 3 of 4 subjects. Transaminase levels in both subjects of one kindred rose during treatment. These limited, preliminary observations suggest that S-adenosylmethionine may be ineffective in the therapy of benign recurrent intrahepatic cholestasis and may be hepatotoxic in some patients.