An improved understanding of bile acid physiology is a prerequisite for the construction of an acceptable model for describing plasma clearance of bile acids. The aim of this study was to determine the extent of reflux unconjugated cholic acid from the liver to the plasma in subjects with normal liver function. The clearance of a bolus injection of unconjugated 14C-cholic acid was studied in four subjects using samples collected simultaneously from a peripheral and a hepatic vein. Hepatic extraction ratios calculated directly from the data were found to be essentially constant during the 20 min following injection, with average values of 0.60-0.72. This indicates that reflux did not occur significantly in the subjects investigated. These results are interpreted as favouring a model in which exchange of unconjugated 14C-cholic acid occurs between the plasma and a peripheral compartment with final removal from the plasma to the liver.