The kinetics of unconjugated 3H-bilirubin are described in 25 healthy dogs and 35 dogs with spontaneous hepatobiliary or haemolytic disease, using a two-compartment model. The bilirubin production rates from erythrocyte degradation (PE), ineffective erythropoiesis (PI) and catabolism of hepatic haemoproteins (PL), were derived from the incorporation of 14C-glycine into haemoglobin and stercobilin. These combined measurements permitted an integral survey of bilirubin metabolism in health and disease. The concentration of unconjugated bilirubin in plasma and its fraction of total bilirubin levels were similar in hepatic and haemolytic disorders. This was explained by the highly increased bilirubin production rates in both types of disease. In addition, the hepatic bilirubin clearance was severely impaired in fulminant hepatitis and in cirrhosis, and moderately decreased in the other hepatobiliary diseases and in primary haemolysis. The erythrocyte lifespan was reduced in all animals but one. In addition to haemolysis, the contribution of PI and PL was variable, and in two dogs PL was the principle source of highly increased bilirubin production rates. These data indicate that the concentration of unconjugated bilirubin in plasma or its fraction of total pigments is unreliable in the discrimination of canine hepatobiliary disease from haemolytic disorders.