The influence of various immunoregulatory substances was studied in lymphocyte cultures derived from patients suffering from systemic lupus erythematosus (SLE) by using the model of spontaneous secretion of polyclonal immunoglobulin G (IgG)/immunoglobulin M (IgM) and anti-DNA autoantibodies. Compared with healthy donors, lymphocytes derived from patients with active SLE disease showed an elevated secretion of total IgG as well as anti-DNA-IgG in vitro, which was associated with an increase in the proportion of activated (HLA-class II +) T cells in their peripheral blood. Recombinant interferon-gamma increases the total IgG/IgM as well as anti-DNA-IgG/IgM secretion, which suggests that it has a possible role in the pathogenesis of SLE disease. Recombinant interleukin-2 and prostaglandin E2 normalize the high, spontaneous total IgG secretion, but elevate anti-DNA-IgG/IgM secretion. These results suggest that autoreactive B-cell clones are regulated differently in SLE patients. Cyclosporine inhibits total IgG/IgM secretion in all patients and anti-DNA-IgG/IgM secretion in six of eight patients. The possible therapeutic use of such immunomodulatory substances in SLE disease is discussed.