Several risk factors have been reported that may favour the development of chronic rejection. From October 1988 to December 1993, 97 liver transplants with survival of more than 3 months were included in the study. Fifty-two patients (54.1%) had chronic hepatitis C virus (HCV) infection before liver transplantation. Immunosuppression consisted of cyclosporine A and prednisone, whereas 14 patients received FK 506 and prednisone. Severe graft HCV reinfection was present in 32 patients (61.5%) after liver transplantation and chronic graft hepatitis C was found in 26 cases at the end of the study. Chronic rejection occurred in 8 of 97 allografts (8.25%); 5 presented chronic rejection and concomitant chronic graft hepatitis C. The incidence of chronic rejection in patients with HCV infection before liver transplantation (9.6%) did not differ when compared with the negative HCV patients (6.6%). However, when the 26 cases that developed graft dysfunction due to chronic hepatitis C after liver transplantation were considered, 5 presented chronic rejection, a significantly higher incidence than in the remaining patients (3 of 71) (Yates chi-square test: P < 0.05). In our experience, there appears to be a relationship between the development of chronic rejection and chronic hepatitis C in the graft after liver transplantation.