The accumulation of false neurotransmitters such as octopamine and depletion of true neurotransmitters such as dopamine have been purported to play a pathogenetic role in portal systemic encephalopathy (PSE). Therefore, we measured plasma prolactin, a known sensitive indicator of functional dopamine activity in man, in an attempt to evaluate dopaminergic function in 21 patients with alcoholic liver disease and PSE and several control groups. Subjects with PSE had markedly elevated prolactin levels (P less than 0.01) when compared to all control groups. Moreover, patients with PSE were divisible into two groups, 12 having mildly increased prolactin levels and 9 having markedly elevated levels. Although the degree of PSE was similar in both groups, those PSE patients with the higher prolactin values had significantly greater derangement of serum albumin, bilirubin, prothrombin time, and also had a higher mortality (100%). These data: (1) provide evidence consistent with the hypothesis of altered neurotransmitter function in individuals with chronic alcoholic liver disease, particularly those manifesting evidence of PSE; (2) suggest that altered dopamine function in chronic liver disease may have pathophysiologic significance as judged by altered hormone release; (3) demonstrate that a markedly elevated plasma prolactin level in individuals with PSE carries an ominous prognosis; and (4) suggest a possible role for the plasma prolactin in the selection and monitoring of PSE patients who are to be treated with agents aimed at correcting neurotransmitter abnormalities.