Previous studies have shown that S-adenosylmethionine (SAMe) counteracts oestrogen-induced bile secretion failure. In order to confirm this anticholestatic activity, we conducted a single-blind clinical trial comparing SAMe with placebo in the treatment of women with intrahepatic cholestasis of pregnancy (ICP). Thirty patients in the last trimester of pregnancy were randomly assigned to receive either SAMe (800 mg/day i.v.) or placebo until delivery for a mean period of 18 days. After SAMe, the women exhibited significantly (p less than 0.01) lower levels of total bile acids, serum conjugated bilirubin and aminotransferases with respect to pretreatment levels as well as to the corresponding values of the placebo group. In addition, SAMe significantly reduced pruritus whereas placebo was ineffective. No adverse reactions on mother or child were recorded during SAMe treatment, and the follow-up of these cases showed an incidence of premature labour (earlier than 37 weeks of gestation) in 2 out of 15 vs 5 out of 15 cases in the placebo group. In conclusion, these findings document that SAMe is more effective than placebo in ameliorating subjective and objective parameters of ICP.