A simplified technique for the measurement of bile-acid pool size and synthesis rate has been developed in patients with liver disease. Isotope dilution studies in blood and bile were performed after intravenous injection of [24-14C]cholic acid with radioimmunoassay for the measurement of the bile-acid concentration. The interpolated pool sizes and synthesis rates, determined from results from both blood and and bile, were not significantly different. The concentration of bile acids in the blood of healthy controls was not sufficiently elevated to permit application of this technique. Three out of six patients with cirrhosis had a markedly reduced pool size compared with that of controls, whereas those with cholestasis had an unchanged pool size. The daily synthesis rate was reduced in both groups. Liver disease caused a redistribution (0.5-16%) of the bile-acid pool to the blood, which was associated with enhanced urinary excretion of cholic acid and its metabolites.