Forty-four asymptomatic patients infected with human immunodeficiency virus type 1 (HIV-1), who had 200-799 CD4 cells/microL, received oral prednisolone (0.5 mg/kg for 6 months; 0.3 mg/kg thereafter). After 1 year of treatment, no major side effect or AIDS events had occurred. The percentage of DR+ and CD25+ phenotypes in CD4 T cells decreased significantly as did levels of serum IgG, IgA, and beta 2-microglobulin. Serum p24 antigen and HIV RNA levels remained stable. CD4 cell counts increased significantly at all time points (median increase at 1 year, 119 cells/microL). Peripheral blood mononuclear cell apoptosis after overnight stimulation with anti-CD3 monoclonal antibodies was strongly inhibited at all times. In asymptomatic seropositive patients, immunotherapy for 1 year with glucocorticoids was safe and led to sustained increases in CD4 cell counts and to improvement or stabilization of other biologic markers of disease activity.