The cholesterol-lowering effect of portacaval anastomosis in homozygous familial hypercholesterolemia suggested a study of lipid metabolism in cirrhotic patients after portasystemic anastomoses. Fasting serum cholesterol, triglycerides, insulin, and glucagon levels were obtained in 20 patients with alcoholic cirrhosis and portacaval anastomosis, and in 21 nonshunted subjects with cirrhosis. After 100 g of glucose, given orally, insulin and glucagon levels were measured. In the shunted patients serum cholesterol was higher than in the nonshunted subjects, 240 +/- 15 mg per 100 ml (mean +/- 1 SEM) versus 180 +/- 13 mg per 100 ml, P less than 0.01. Triglycerides were normal in both groups. Fasting insulin was elevated to a greater extent in the shunted patients with cirrhosis (36 +/- 5 muU per ml) than in the nonshunted patients (22 +/- 4 muU per ml), P less than 0.05. Two hours after glucose, insulin levels were also elevated to a greater extent in the shunted subjects (304 +/- 50 muU per ml) than in the nonshunted subjects (167 +/- 29 muU per ml), P less than 0.03. Fasting glucagon (corrected for interference factor) was elevated to a greater extent in the shunted subjects (204 +/- 35 pg per ml) than in the nonshunted subjects (80 +/- 19 pg per ml), P less than 0.01. The explanation for serum cholesterol elevation after surgical shunting in cirrhotics is unknown. Two possible hypotheses--the differential action of insulin and glucagon on cholesterol metabolism and the effects of shunting on the cirrhotic liver--are discussed.