Glucagon and insulin metabolism was studied in 9 cirrhotic patients and 4 non-cirrhotic controls. Net output of glucagon and insulin into portal circulation was calculated from difference between portal venous and systemic arterial concentrations multiplied by portal plasma flow. Metabolic clearance rate was also calculated as the ratio of the output to systemic concentration. Portal blood flow was measured by the continuous local thermodilution method. The results were as follows: 1) Arterial glucagon concentration was elevated in liver cirrhotics compared with non-cirrhotic-controls. Glucagon output in cirrhotics was higher than in controls [46.3 +/- 11.8 vs. 13.2 +/- 2.5 ng/min (mean +/- SEM), p less than 0.05]. Metabolic clearance rate of glucagon was not significantly different between the two groups. 2) There was a significant correlation between glucagon output and portal venous concentration of norepinephrine (r = 0.625, p less than 0.05). 3) Insulin levels in systemic arterial blood were higher in cirrhotic patients than non-cirrhotic subjects. Insulin output was not significantly different between the two groups, however, metabolic clearance rate of insulin in cirrhotics was reduced in comparison with the controls (274.5 +/- 44.3 vs. 557.7 +/- 108.6 ml/min, p less than 0.05).