Although the protracted use of total parenteral nutrition (TPN) in infants is known to predispose to cholestasis, which in certain instances may not be reversible, failure to understand the pathogenesis of this condition has hindered the development of an effective medical treatment. That surgical treatment may reverse this process in selected patients is the subject of the present report. Two premature infants and one term infant, with short bowel syndrome acquired in infancy, developed conjugated hyperbilirubinemia following institution of balanced TPN. Infectious and metabolic etiologies for the jaundice were ruled out. No excretion of 99mTc-labeled DISIDA from the biliary tree was demonstrable 24 hours following injection by nuclear scintigraphy, despite the absence of extrahepatic biliary obstruction by abdominal sonography. When all conventional medical methods of managing the problem failed, exploration was performed. Intraoperative cholangiography showed normal intrahepatic and extrahepatic biliary ducts in each instance. Irrigation of the biliary tree with normal saline solution was then performed. In all cases, liver biopsies were obtained that were consistent with TPN-associated cholestasis and in all cases, jaundice resolved promptly following operation. We conclude that intractable cholestasis associated with TPN, regardless of its etiology, is a functional abnormality of biliary excretion that may respond in selected patients to irrigation of the biliary tree with radiographic dye and/or normal saline solution.