This study examines the role of sex hormones in modulating the expression of autoimmunity in NZB x NZW Flmice. Male sex hormones were found to retard disease. Differekes were noted between prepubertally and postpubertally altered males and females. The presence of male sex hormones prepubertally was associated with marked retardation of the development of antibodies to DNA. Prepu-bertal but not postpubertal castration of males led to significant acceleration in anti-DNA production. Nevertheless, administration of male sex hormones to females retarded the development of fatal glomerulonephritis, even when given postpubertally. These results suggest that manipulation of sex hormones may be used to modify the expression of autoimmunity.