Patients with active systemic lupus erythematosus (SLE) in the circulation have a selective increase of a subset of the CD4+ helper/inducer T cells bearing HLA-DR+, major histocompatibility complex class II antigens. We studied prednisolone-induced alterations of HLA-DR+, CD4+, and CD8+ T-cell subsets in three patients with active SLE. Prednisolone therapy was accompanied by a drastic reduction in circulating HLA-DR+, CD4+ T-cell subsets, serum anti-DNA titre, normalization of the serum immunoglobulin profile, and CD4+ T-cell responses to phytohaemagglutinin and concanavalin A. These changes in immune functions were associated with eventual improvement in the clinical condition of active SLE. A low percentage of HLA-DR+, CD8+ T-cell subsets was present in the circulation, which was not changed by prednisolone therapy. These results suggest that HLA-DR+, CD4+ T-cell subsets play a major role in the pathogenesis of active SLE, and that prednisolone-induced immunosuppression in this disease is mediated by changes in the HLA-DR+, CD4+ T-cell subsets in circulating blood.