A second generation hepatitis C virus recombinant immunoblot assay (RIBA) was used to screen stored perioperative serum from 641 renal allograft recipients. One hundred and nine (17%) were anti-HCV positive at the time of transplant. RIBA positivity was found to be an independent predictor of post-transplant liver disease in a logistic regression model (P < 0.05). Moreover, RIBA positive patients were at greater risk for infectious events (P = 0.03) and rejection episodes (P = 0.002). The cumulative dose of antilymphoblast globulin administered as induction therapy was an independent predictor of post-transplant liver disease in a dose response relationship. Qualitative PCR showed that 74% of the perioperative RIBA positive patients had detectable HCV RNA in a current serum sample. Further, quantitative HCV RNA analysis with a competitive template PCR and HCV strain identification by restriction fragment length polymorphism demonstrated a large range of HCV RNA copies/ml of serum and three different HCV strains (BK, Hutch and HCV-1). Neither quantity of HCV RNA nor strain type correlated with abnormal transaminases post-transplant. As yet, there has not been an effect of anti-HCV status on actuarial patient and graft survival. This study suggests that anti-HCV is not a contraindication to renal transplantation; however, we would recommend that the pre-transplant evaluation of the anti-HCV positive patient include a liver biopsy to properly stage the disease. Close post-transplant follow-up is required in view of the increased risk for infection and rejection.