We report the clinical and radiologic findings and course of two patients who developed drug-related biliary sclerosis during hepatic artery infusion of floxuridine. If severe and persistent jaundice develops during the course of regional hepatic infusion of floxuridine, and obstructive component in the biliary tree must be suspected and investigated by endoscopic retrograde cholangiography. Regional infusion therapy should be stopped immediately. Surgical treatment of the obstructing lesion is avoided unless cholangitis occurs or jaundice persists for more than 3 months and a surgically correctable lesion exists.