The development of anti-nuclear antibody (ANA) and glomerulonephritis (GN) in autoimmune NZB x NZWF1 mice was suppressed by persistent lactic dehydrogenase virus (LDV) infection. This observation was used to study a possible pathogenetic role for the toxic oxygen radical, superoxide anion (O2-), in the progression of ANA and GN. Compared to macrophages from NZB x NZWF1 mice with LDV infection, macrophages from uninfected NZB x NZWF1 mice exhibited an age-related and drastic increase in O2- production in association with the development of the ANA and GN (representing the late stage of disease). NZB x NZWF1 mice with or without LDV infection were then given the O2- scavenger superoxide dismutase (SOD) during the late stage of the disease. Treatment of uninfected NZB x NZWF1 mice with SOD (10,000 units/mouse/day for 3 weeks) protected animals from the development of ANA and GN. SOD treatment also suppressed the development of the lesions in NZB x NZWF1 mice with LDV infection. Our findings suggest that O2- may, at least in part, contribute to the development of ANA and GN in the late stage of disease, and that decreased O2- production in NZB x NZWF1 mice with LDV infection may be responsible for the suppression of the development of ANA and GN in the late stage of the disease.