The effects of oral BCAA supplementation on fasting levels of prolactin and estradiol were retrospectively analyzed in frozen plasma samples of patients with cirrhosis and chronic hepatic encephalopathy, taking part in a 3-month randomized, double-blind trial. Twenty-five patients had received 0.24g of BCAA per kg body weight, 24 had received an equinitrogenous amount of casein, in addition to a diet providing 0.7-1.0 g/kg of protein. Thirty-eight were males, 11 post-menopausal women. Fasting prolactin did not show any change in the BCAA group, where mental state significantly improved. In the casein group plasma prolactin increased by nearly 50% during the 3-month period. Similarly, estradiol concentrations were unchanged during BCAA supplementation, and increased during casein treatment. The analysis of variance demonstrated significant differences between the 2 treatments. Liver function tests and nutritional parameters (albumin, transferrin, urinary creatinine) supported a superiority of BCAA over casein. These data suggest that the favorable effects of BCAA on mental state are not mediated by changes in cerebral neurotransmission, but are due mainly to maintained liver function, possibly related to improved nutrition.