HCV is the principal etiologic agent of post-transfusion (PTH) hepatitis. The incidence and course of HCV hepatitis in liver transplant recipients is not well established. To resolve this information deficit, all records of recipients of single liver transplant (OLTx) between March 1986 and March 1990 at the University of Pittsburgh in whom both the donor and recipients' pre-OLTx sera were available (n = 516) were reviewed. All sera were assayed for HCV antibody using a second generation ELISA method developed by Abbott Laboratories. On the basis of the anti-HCV status of the donor and recipient pre-OLTx sera, four groups could be classified: group I (donor-, recipient-) n = 375; group II (donor-, recipient+) n = 111; group III (donor+, recipient-) n = 25; and group IV (donor+, recipient+) n = 5. Post OLTx liver biopsies were obtained for a clinical indication in 473 of these 516 patients. The prevalence of anti-HCV among recipients pre-OLTx was 22.5% (116/516) which is three times greater than the 5.8% (30/516) prevalence in the donors. Histologic hepatitis not ascribable to any cause other than HCV occurred in 76/516 (15%) recipients: 42 in group I; 28 in group II; 6 in group III and none in group IV. The overall risk of HCV hepatitis at 6 months, 1 year and 2 years post-OLTx was 4.8% (25/516), 7.6% (39/516) and 10. 1% (52/516), respectively. At each of these time intervals, no significant difference between groups for the prevalence of HCV hepatitis was evident. Twenty-one of the 76 recipients (28%) with histologic HCV hepatitis developed CAH, of which 9 were in group I, 11 in group II and 1 in group III. Two of 9 patients in group I developed cirrhosis. The 2-year graft survival and patient survival rates for each group ranged from 60 to 80% and 60 to 100%, respectively, with the poorest results in group III and the best results paradoxically in group IV. These data demonstrate that: (i) the overall rate of developing HCV hepatitis post OLTx is 15%, ranging from 0 to 25% in groups I to IV (ii) progression to CAH and cirrhosis can occur in HCV infected allografts at 2-5 years but is infrequent and (iii) presence of antibody to HCV pre-OLTx in either the donor or the recipient does not appear to place the recipient at an excessive risk for the development of HCV hepatitis.