1. Fasting concentrations of C, CD and D were determined in systemic and portal venous serum in gallstone patients and controls (patients with adenomyoma of the gallbladder) undergoing cholecystectomy. No differences were observed between the two groups either in systemic or portal serum concentrations of the bile acids or in their hepatic uptake. Ketonic bile acid concentrations amounted to 9% and 8% of the non-oxidized bile acids in the systemic and portal circulation, respectively. 2. Fasting systemic and portal venous serum concentrations of bile acids were measured in gallstone patients fed with C and CD prior to cholecystectomy. Treatment with CD increased the total portal inflow of bile acids by 60%, whereas C treatment did not alter this total inflow compared with controls. This difference may partly explain why hepatic bile is unsaturated during treatment with CD, but not with C. 3. The postprandial concentrations of bile acids were determined in the systemic and portal venous circulation in cholecystectomized patients. The systemic venous bile acid level reflected the portal venous level. The estimated hepatic uptake of the individual bile acids was highly efficient and could not be saturated during maximal physiological portal inflow to the liver. The existence of a lymphatic transport of bile acids, calculated to correspond to about 0.2% of the portal transport, was demonstrated in four patients undergoing renal transplantation. 4. Cholestyramine treatment was shown to reduce the plasma cholesterol level in patients with familial hypercholesterolaemia without lowering the fasting systemic level of total bile acids. Nor did this treatment reduce the fasting portal inflow of total bile acids. The total bile acid concentration in healthy volunteers during treatment showed a 40% reduction postprandially, but not in the fasting state, indicating that the effect of cholestyramine on hepatic cholesterol metabolism is the consequence of a reduced postprandial inflow of portal bile acids. The effects of the loss of the active site of bile acid absorption on the postprandial serum bile acid pattern were studied in patients with ileal resections. In general, the postprandial response of C was reduced whereas that of CD remained less affected.