The plasma clearance of an i.v. bolus of chenodeoxycholic acid (10 μm per kg) was determined in rabbits with graded degrees of hepatocellular necrosis produced by i.p. injection of carbon tetrachloride. Plasma chenodeoxycholic acid levels were determined by radioimmunoassay, and the volume fraction of necrosis was quantitated by a computerized (Quantimet 720) system. Impaired plasma clearance was observed only when necrosis was extensive, and the volume fraction of necrosis >34%. In contrast, measurement of fasting plasma chenodeoxycholic acid concentration was more sensitive, and elevated levels were associated with a mean volume fraction of necrosis of 12.5%. This study reinforces the conclusion based on clinical studies that measurement of fasting bile acid concentration is a more sensitive discriminant of hepatic dysfunction than is measurement of the plasma clearance of an i.v. bolus of bile acid.