Neuropsychological status, hepatic function, and nitrogen metabolism were quantitatively assessed in 30 cirrhotic patients 1 to 5 years after portal-systemic shunt surgery to determine the frequency of behavioral deficits and their relationship to existing metabolic abnormalities. Evaluation consisted of three measures of liver function (Child's score, galactose elimination capacity, and antipyrine clearance), three tests of nitrogen metabolism (fasting venous ammonia (NH3), ammonia tolerance test, and maximal rate of urea synthesis), neurological examination, EEG, and 11 psychometric indices. Control values for the tests of hepatic function, nitrogen metabolism, and psychometric performance were established in a group of 14 normals matched to the cirrhotics for age, sex, and education. All patients were normal by conventional neurological and mental status examinations. Ten patients (33%) had EEG's compatible with hepatic encephalopathy; 18 patients (60%) showed impaired performance on one of the psychometric tests (Reitan Trail B). NH3 was inversely correlated with four psychometric tests and maximal rate of urea synthesis was directly related to five tests. In contrast, ammonia tolerance score was not significantly associated with any of the neuropsychological variables and the three quantitative measures of hepatic function together only correlated with five tests. Five cirrhotic patients with hyperammonemia and impaired psychometric tests were treated for 7 days with a protein-free diet. In all subjects, hyperammonemia and neuropsychological abnormalities improved or disappeared. Average values for the psychometric tests in 15 alcoholic subjects without liver disease did not differ significantly (P > 0.05) from the normal group. We conclude that the majority of cirrhotic patients after portal-systemic shunt operations have demonstrable neuropsychological deficits. The severity of impairment appears to be related more to status of nitrogen metabolism than to level of over-all hepatic function.