It is well recognized that hepatitis recurs in virtually all patients who undergo orthotopic liver transplantation for cirrhosis secondary to chronic hepatitis C (HCV). The present report describes the biochemical and histologic findings of recurrent hepatitis in 25 such patients. One patient was found to have hepatocellular carcinoma at the time of OLT and was excluded from further analysis. All post-OLT laboratory values were reviewed. Liver biopsies were performed on protocol 6, 12, 24, and 36 months following OLT. Additional biopsies were performed as necessary to evaluate abnormalities in serum liver chemistries. A total of 104 biopsies was obtained; hepatitis consistent with recurrent HCV was present in 68 (65%). Other biopsy findings included cytomegalovirus hepatitis; acute, chronic, or resolving rejection; cholestasis with or without an underlying hepatitis; steatosis, and centrilobular necrosis. Histologic hepatitis appeared in all patients within 12 months following OLT. Despite these histologic findings, serum ALT was normal for prolonged periods in over 50% of such patients. In all cases this hepatitis was mild and did not progress over a mean follow-up of 22 months (maximum 44 months), as judged by Knodell histologic activity score (mean score: 4.0 +/- 0.3). Five patients developed cholestatic jaundice, far out of proportion to the degree of histologic hepatitis. In 2 patients this was secondary to chronic rejection. The other 3 patients had drug-induced cholestasis that resolved after various medications were discontinued. HCV did not contribute to graft dysfunction in any of the 24 patients. To date, our data suggest that post-OLT hepatitis in patients with preexisting HCV is a relatively benign process. Severe cholestatic jaundice in such patients is not secondary to HCV, and should stimulate a search for other possible causes of graft dysfunction. The long-term consequences of recurrent HCV following hepatic transplantation remain to be determined.