Portacaval anastomosis (PCA) lowered by 50% the cholesterol concentration in the plasma of rats. The free and esterified cholesterol contents in the lipoproteins were decreased with the very low density lipoproteins most affected (-85%). Cholesterol concentration as total content in the liver was reduced. The major change in the cholesterol metabolism, as studied with an isotopic equilibrium method, was the decrease in the intestinal absorption coefficient of dietary cholesterol (56.0 +/- 2.7% instead of 73.3 +/- 1.9% in controls). The rate of cholesterol transformation into bile acids was decreased (10.5 +/- 0.3 vs 14.5 +/- 0.5 mg/day/rat in controls). The rate of internal secretion of cholesterol was slightly reduced while the rate of fecal external secretion was increased, suggesting that the synthesis of cholesterol by extra-digestive tissues (including liver) was reduced after PCA. The effects of PCA on cholesterol metabolism were similar to those described for glucagon administration. Since this shunt results in hyperglucagonemia, it is suggested that this hormonal perturbation was the main factor involved in the modifications of cholesterol metabolism after PCA. Moreover, mesentericocaval anastomosis, which shunts only the intestinal blood and allows the pancreatic hormones a normal transport through the liver, did not significantly modify cholesterol metabolism. Only cholesterolemia (-28%) and the absorption coefficient of dietary cholesterol (66.0 +/- 2.3%) were slightly reduced.