NZB/NZW F, hybrid mice were treated with pharmacologic doses of prostaglandin El (PGE,) (200 pg subcutaneously either once or twice daily) from 6 through 52 weeks of age. PGE,-treated mice were protected against development of anemia, clinical nephritis, and death. At 52 weeks, 18 of 19 treated mice were alive, whereas only 2 of 19 untreated control mice were alive. None of the 10 mice treated with PGE, twice daily exhibited significant (>2+) proteinuria at 1 year of age. PGE, 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 PGE, is begun at 24 weeks, an age at which mice already show evidence of nephritis. Thus all 6 mice treated with PGE, (200 pg sc twice daily) from 24 weeks were alive a t 52 weeks, whereas only 2 of 6 untreated control mice were alive. The mechanisms whereby PGE, treatment influences the course of disease in NZB/NZW mice are not known.