A 58-year-old Japanese man was admitted to our hospital with appendicitis and marked unconjugated hyperbilirubinemia (11.6 mg/dl). The jaundice worsened following appendectomy, and the direct-reacting bilirubin increased, probably due to the ceftizoxime administered postoperatively. Bilirubin diglucuronide was the main component of the serum direct-reacting bilirubin (51%) in serum measured by liquid chromatography. Because the discontinuation of ceftizoxime did not markedly improve the jaundice, epomediol, 200 mg tid, was administered orally. There was a marked decrease of serum bilirubin with an increase in the delta bilirubin/(conjugated bilirubin + delta bilirubin) ratio. After improvement of jaundice to below the pre-surgical level (4.4 mg/dl), we analyzed the duodenal bile for bilirubin fractions; those showed a marked reduction in bilirubin diglucuronide and a marked increase in bilirubin monoglucuronide, which was consistent with type II Crigler-Najjar syndrome. A marked increase of bilirubin diglucuronide in serum of this patient during cholestasis suggests that bilirubin conjugation proceeds in this syndrome when excretion of conjugated bilirubin decreases.