Plasma methionine enkephalin is increased in liver disease and may contribute to some of the clinical manifestations of hepatic failure. To determine if another 'small' opioid peptide is increased in the plasma of patients with liver disease, leucine enkephalin was measured by radioimmunoassay. Its plasma concentration was raised approximately five-fold in patients with acute liver disease (median 1490 pmol/l, range 830-2420) and three-fold in patients with cirrhosis with ascites (960 pmol/l, 470-2900), compared with disease controls (325 pmol/l, 180-740) and healthy controls (305 pmol/l, 180-560). The increase in plasma leucine enkephalin was proportional to the degree of liver damage, as judged in the patients with acute liver disease by its correlation with the prothrombin time (r = 0.691, p less than 0.01) and alanine aminotransferase (r = 0.502, p less than 0.05), and in the patients with cirrhosis by its negative correlation with the plasma albumin (r = -0.743, p less than 0.001). It is unclear whether the raised plasma leucine enkephalin in liver disease is a consequence of diminished hepatic inactivation, increased secretion from sympathetic nerves and adrenal glands, or both.