Controversy exists regarding the impact of pretransplantation HCV infection on the outcome of renal transplantation. We compared the prevalence of posttransplantation liver disease and graft and patient survival among kidney transplant recipients with and without anti-HCV at the time of transplantation. Pretransplantation sera from 103 randomly selected recipients of kidneys from anti-HCV-negative donors were tested for anti-HCV using a second generation ELISA. Twenty-three (22%) were positive for anti-HCV and 80 (78%) were negative. Anti-HCV-positive recipients had a longer time on dialysis (P = 0.003) and had a higher number of previous transplants (P = 0.01). Further, 61% of anti-HCV-positive patients had a history of liver disease compared with 13% of anti-HCV-negative patients (P < 0.001). HCV RNA was detected in the pretransplantation serum in 61% of anti-HCV positive recipients compared with 5% of anti-HCV-negative recipients (P < 0.001). Clinical follow-up on both anti-HCV-positive and -negative patients was obtained until December, 1993. Median posttransplantation follow-up among recipients with anti-HCV prior to transplantation (45 months) was shorter (P = 0.05) than that for recipients without anti-HCV (66 months). For recipients with anti-HCV prior to transplantation, the relative risk of posttransplantation liver disease was 5.0 (95% confidence intervals of 2.4 to 10.5); the relative risk of graft loss was 1.3 (95% confidence intervals of 0.6 to 2.6); the relative risk of death was 3.3 (95% confidence intervals of 1.4 to 7.9), and the relative risk of death due to sepsis was 9.9 (95% confidence intervals of 2.6 to 38.3). The results of this study demonstrate that pretransplantation HCV infection is associated with an increased risk of liver disease and death after renal transplantation. These results raise the question of whether anti-HCV-positive patients on dialysis should be offered renal transplantation as opposed to continuing dialysis.