Complications of endoscopic retrograde cholangiography specific to patients with primary sclerosing cholangitis have not yet been reported. We observed transient rises of serum bilirubin after diagnostic endoscopic retrograde cholangiography in five of 15 patients and persistent rises in three of 15 patients with primary sclerosing cholangitis examined consecutively by endoscopic retrograde cholangiography from 1985 to 1990. Deterioration of cholestasis was particularly associated with advanced disease. Seven of eight patients with deterioration after endoscopic retrograde cholangiography had septal fibrosis (stage III) or cirrhosis (stage IV) and a priori elevated serum bilirubin levels. In contrast, all patients with no deterioration of cholestasis following endoscopic retrograde cholangiography had early histological changes (stage I-II), and all but one patient had normal serum bilirubin levels. We conclude that the potentially harmful effects on biliary excretion must be taken into account when the use of endoscopic retrograde cholangiography is being considered in patients with advanced primary sclerosing cholangitis.