Chronic hepatitis B virus (HBV) is associated with increased morbidity and mortality in patients with chronic renal failure (CRF) and renal transplant recipients. Lamivudine (3TC) has been shown to be a potent inhibitor of HBV replication. It appears to be safe and effective in patients with CRF, though experience is still limited. We describe 4 patients with CRF on hemodialysis who showed a rapid and full response to 3TC, administered for a median of 10 months. All patients had serum alanine transferase (ALT) levels 3 to 6 times the upper limit of normal prior to treatment, and different degrees of histologic inflammatory activity (Knodell score 4 to 8, median 6). All were serum HBsAg- and HBeAg-positive, with serum HBV DNA 1-3.9 x 107 copies/mL (median 1 x 107 copies/mL). Within 4 to 8 weeks of initiation of therapy, HBV DNA became undetectable and serum ALT normalized. Serum HBeAg disappeared in all 4 patients, with the emergence of anti-HBeAb in 3 of them. Three patients also lost HBsAg with the evolution of a protective anti-HBsAb titer. One patient has already undergone successful kidney transplantation with no evidence of HBV recurrence (serum HBV DNA negative) 16 months postoperatively. Although our study sample is small, these data suggest that 3TC can induce a complete biochemical, virological and serological response in patients with CRF and HBV infection. Its use may enable safe kidney transplantation in selected patients.