Features characteristic of the Crigler-Najjar syndrome (type II) are described in an adolescent boy with severe congenital unconjugated hyperbilirubinemia. Bilirubin encephalopathy developed only in early puberty after surgery and fasting, coincident with a dramatic rise in serum bilirubin, which responded to intensive therapy. Fasting was later shown to increase markedly the serum bilirubin levels and probably was a major factor in precipitating the initial acute event. One year later, while the patient was in a metabolic steady state, the secretion rate of bilirubin was measured by aduodenal marker-perfusion technique, and the nature of the secreted bilirubin conjugates was characterized. Total bilirubin secretion rates were low, 4.39 mg per hr and 4.44 mg per hr on two separate studies. The major pigment detected in bile was bilirubin monoglucuronide. Bilirubin diglucuronide comprised only a minor fraction of the pigments, and other conjugates were not detected. The present study documents a reduced biliary bilirubin secretion and suggests that the addition of the second glucuronic acid moiety to the bilirubin molecule may be defective in Crigler-Najjar syndrome (type II).