In order to investigate whether the variations in prolactin (PRL) secretion found in patients with liver cirrhosis are related to the derangement of neurotransmitter metabolism, serum PRL levels were measured in 8 patients with hepatic encephalopathy (a condition where neurotransmission is severely deranged), in 10 patients with liver cirrhosis but without encephalopathy and in 10 control subjects under control conditions and in response to nomifensine, levodopa and synthetic TRH administration. Inhibition of endogenous catecholamine reuptake by nomifensine was able to significantly reduce PRL levels in normal subjects and in patients with liver cirrhosis, whereas only one out of 8 patients with hepatic encephalopathy showed a reduction in PRL levels. On the contrary, levodopa administration was able to reduce PRL secretion in all the subjects studied. PRL release by TRH was greater in patients with liver disease than in controls. The results seem to indicate that the derangement in neurotransmitter metabolism which occurs in liver cirrhosis is one, but not the sole cause of alterations of PRL secretion in liver cirrhosis. The failure of nomifensine to depress PRL is an early finding in the course of encephalopathy and may be of diagnostic value.