Background: The hepatitis B virus (HBV) vaccine has resulted in a decline in the incidence of HBV carriage and hepatocellular carcinoma in southeast Asia. Vaccine efficacy in Africa has not been adequately assessed. Objective: To report on the impact of HBV vaccination in South Africa on HBV-associated membranous nephropathy (MN) over 6 years. Methods: King Edward VIII Hospital in Durban is the only tertiary referral center for the province of KwaZulu-Natal for children with renal, diseases. The HBV vaccine was introduced into the South African Expanded Programme on Immunisation on April 1, 1995; vaccine coverage rates between April 1, 1995, and December 31, 2001, for children for the first, second, and third doses were 85.4%, 78.2%, and 62.0%, respectively. Hepatitis B virus status Was determined using a radioimmunoassay (January 1, 1984-March 31, 1991) or an enzyme-linked immunosorbent assay. Membranous nephropathy was confirmed by the results of a renal biopsy. The hospital average annual incidence of HBV-associated MN was compared before and after vaccination and according to age groups. Results: Between January 31, 1984, and December 31, 2001, there were 119 children with HBV-associated MN; their mean age was 7 years (range, 1-14 years), and 101 (84.9%) were males. The average annual rate ratio per 10(5) child population was 0.25. The overall incidence rate ratio showed a significant decrease from January 1, 2000, to December 31, 2001, compared with the preimmunization period (January 1, 1984-December 31, 1994) (incidence rate ratio, 0.12; 95% confidence interval, 0.03-0.50). Children from birth to the age of 4 years experienced no disease after 1998. Children aged 5 to 10 years showed a significant decrease in 2000-2001 compared with the prevaccination years (incidence rate ratio, 0.19; 95% confidence interval, 0.05-0.80). Conclusion: The HBV vaccine, even at low coverage for the full South African Expanded Programme on Immunisation schedule, reduced the hospital incidence of HBV-associated MN over 6 years.