While it is generally recognized that females show enhanced cell-mediated and antibody responses to antigenic stimulation, the physiological basis for this observed sexual dimorphism of the immune response is not well understood. We report here studies on the effects of androgen deficiency on the peripheral immune system. Intact male mice were compared to animals castrated 3-4 months previously. Phenotypic characterization of thymocyte and lymphocyte subpopulations was carried out using dual-colour flow cytometry. In vitro production by spleen cells of interleukin-2 (IL-2), IL-4 and interferon-gamma (IFN-gamma), and levels of total immunoglobulin and autoreactive antibodies was measured by specific immunoassays. In addition to thymic hypertrophy, castrated animals showed significant splenic enlargement, which was largely owing to expansion of the B-cell population. The castrated spleens contained relatively fewer mature T cells than intact controls (P < or = 0.001), but culture supernatants from these spleen cells contained higher levels of IL-2 and IFN-gamma than control cultures (P < 0.04). Levels of in vitro antibody synthesis (IgM, IgG, IgA) were not higher in castrated animals compared to controls, but the castrate spleen cell cultures showed increased levels of production of two autoreactive antibodies, anti-IgG (rheumatoid factor) and anti-thyroglobulin. These data suggest that androgen deprivation results in a relative decrease in the number of mature peripheral T cells, but those which reach the spleen have functional characteristics suggestive of enhanced activation. Dysregulation in the B-cell compartment may be the result of altered effects of T-cell-mediated control.