Of 567 patients receiving renal transplantation at the University of Minnesota between October 1967 and October 1975, 22 developed clinical jaundice. Of these 22, nine died with their initial episode of hepatitis, six died within three months of causes associated with liver malfunction, four developed evidence of chronic hepatic failure and only three totally recovered from their illness. Five had clear evidence of Australia antigen positive hepatitis B, four of cytomegalovirus hepatitis, two of herpes hominis hepatitis, one of varicella zoster hepatitis and three of hepatic failure associated with systemic bacterial and/or fungal sepsis. Two of the 22 patients were thought likely to have cytomegalovirus hepatitis though definite proof was absent and in five patients a clear-cut etiology could not be made. In many of these patients the diagnosis was confounded by the previous presence of HBsAg antigen and the frequent occurrence of a previous or concurrent infection with cytomegalovirus. The role of various drugs including azathio-prine, sulfisoxazole, chlorpromazine, acetominophen, etc., could not be established but major roles for these agents in the face of the many viral and bacterial infections present in these patients is doubted. No clear-cut therapy could be established although it appears safe to discontinue azathioprine for longer or shorter periods of time with or without substitution of cyclophosphamide without serious deterioration of renal function. The problem of hepatic failure in transplant patients is still unsolved and will require a prospective study of etiologic agents and sub-clinical hepatic dysfunction in order to establish even the first principles of clinical-pathological correlation.