NZB/NZW F1 hybrid mice were treated with pharmacologic doses of prostaglandin E1 (PGE1) (200 microng subcutaneously either once or twice daily) from 6 through 52 weeks of age. PGE1-treated mice were protected against development anemia, clinical nephritis, and death. At 52 weeks 18 of 19 treated mice were alive, wherase only 2 of 19 untretreated control mice were alive. None of the 10 mice treated with PGE1 twice daily exhibited significant (greater than 2+) proteinuria at 1 year of age. PGE1 treatment did not prevent development of antibodies to nuclear antigens. The data also suggest that survival of NZB/NZW mice is prolonged when treatment with PGE1 is begun at 24 weeks, an age at which mice already show evidence of nephritis. Thus all 6 mice treated with PGE1 (200 microng sc twice daily) from 24 weeks were alive at 52 weeks, whereas only 2 of 6 untreated control mice were alive. The mechanisms whereby PGE1 treatment influences the course of disease in NZB/NZW mice are not known.