Posttransplant lymphoproliferative disease (PTLD) is associated with immunosuppression and lymphotrophic viral infections. Hepatitis C virus (HCV) has been identified as a risk factor for non-Hodgkin's lymphoma, but no association between HCV and PTLD has been shown. To investigate this possibility, we identified patients with HCV who received their first orthotopic liver transplant at our unit between January 1, 1992, and December 31, 1996, and compared them with contemporary liver transplant recipients without HCV for incidence and risk factors for PTLD and survival. Fifty-seven patients with HCV and 127 patients without HCV were compared. There was no age difference (52 v 53 years; P =.85), but there were more men in the HCV group (man-woman ratio, 2.1:1 v 0.9:1; P =.006). No difference was observed in the follow-up period, graft survival, rejection episodes, or use of different immunosuppressive regimes (P >.05 for all). Four patients with HCV (7%) developed PTLD compared with 1 patient without HCV (0.8%; P =.02). The relative odds for developing PTLD in patients with HCV were 9.5. All patients who developed PTLD were administered OKT3 induction therapy. These data suggest that PTLD may be more prevalent in patients undergoing liver transplantation for HCV-related liver disease who also receive OKT3, and that HCV infection may be a risk factor for developing PTLD.