In an attempt to evaluate the long-term reciprocal impact of renal transplantation on hepatitis B virus infection, we analyzed the clinical, virologic, and pathologic features of 151 HBsAg-positive kidney transplant recipients. The spontaneous disappearance rates of HBsAg, HBeAg, and HBV DNA during a median follow-up of 125 months (range 1 to 320) were 3, 30.6, and 3%, respectively, figures lower than in the general population. A high rate of persistent viral replication (50%) and reactivation (30%) was noted. Noteworthy was the high frequency of histologic deterioration (85.3%), accompanied by cirrhosis in 28% and by hepatocellular carcinoma in 23% of the patients with cirrhosis. Co-infection by hepatitis C and B viruses was significantly associated with histologic worsening. Liver disease was the leading cause of death (36.6%), especially in patients with cirrhosis. Despite persistent viral replication, histopathologic deterioration, and liver-related overmortality, there were paradoxically no significant differences in the survival of these 151 HBsAg-positive compared with 1247 HBsAg-negative kidney recipients--however, allograft actuarial survival was better in the former than in the latter group (P=0.0006). Chronic hepatitis B infection is not a contraindication to renal transplantation in the absence of cirrhosis. The presence of cirrhosis should lead either to dialysis continuation or to a combined liver/kidney transplantation, in the absence of viral replication.