ABSTRACT: Previous experimental and clinical investigations have pointed out a causal relationship between estrogens and the impairment of bile secretory apparatus, resulting in lithogenic bile and cholestasis. Recent studies have also shown that S-adenosylmethionine (SAMe) counteracts both estrogen-induced bile cholesterol supersaturation and intrahepatic cholestasis. The aim of this investigation was to verify whether SAMe could also reverse the abnormalities of some liver function tests that may develop in susceptible women after the intake of estrogen-containing oral contraceptives. Twelve women out of a group of 228 subjects exhibited abnormal blood values of transaminases, antithrombin III or bile acids after two cycles of a contraceptive pill containing 30 meg ethynylestradiol. These subjects volunteered to receive the same contraceptive pill plus oral SAMe (600 mg/day) for another two cycles. Due to the small number of cases who developed abnormal hepatic function tests after oral contraceptive, it was not possible to divide them into a control group who continued on the “pill” plus placebo and a treatment group in whom SAMe was given with the oral contraceptive. In all cases the administration of SAMe induced the normalization of liver function tests. If further clinical trials confirm these findings, it may be possible to propose SAMe administration to women at an increased risk of developing estrogen-related hepatotoxicity.