The role that portosystemic shunting plays in inducing the alterations of glucagon and insulin metabolism, which are observed in chronic liver disease, was studied in a rat model of prehepatic portal hypertension induced by portal vein constriction. Net splanchnic output of the hormones into the portal circulation was calculated from the difference between portal and systemic concentrations multiplied by portal plasma flow. Metabolic clearance rate was calculated as the ratio between output and systemic concentration. Portal blood flow was measured by the radioactive microsphere technique. Glucagon output in the portal vein-ligated rats was higher than in the sham-operated controls (5.9 +/- 1.5 vs. 2.0 +/- 0.2 ng/min, P less than 0.05). The metabolic clearance rate of glucagon was not significantly different between the two groups. Insulin output was not significantly different between the two groups; however, the metabolic clearance rate of insulin in the portal vein-ligated rats was reduced in comparison with the sham-operated group (9.5 +/- 1.5 vs. 18.4 +/- 3.3 ml/min, P less than 0.05). Our results indicate that portosystemic shunting per se is sufficient to cause an increased splanchnic output of glucagon into the portal system and a decreased metabolic clearance of insulin.