We investigated 2H4+ and 4B4+ T cell subsets from the purified CD4+ helper/inducer and CD8+ suppressor/cytotoxic T cells in circulating blood of 15 patients with severe active systemic lupus erythematosus (SLE), 6 patients with inactive SLE, 5 patients with rheumatoid arthritis and seven healthy controls. The percentage of the total CD4+ T cells increased and CD8+ T cells decreased in all patients with active SLE. Of interest, however, all the patients with active SLE and central nervous system (CNS) disease had a selective decrease in the percentage of CD4+ 2H4+ T cell subsets in circulating blood that is responsible for induction of the CD8+ suppressor T cells. This loss of the CD4+ 2H4+ T cells was accompanied by an increase in the CD4+ 4B4+ T cell subsets, that are the true helper/inducers providing help for B cell immunoglobulin production. A marked decrease in the CD4+ 2H4+ cell subsets in the circulating blood of all patients with severe active SLE and CNS disease is related with meaningful functional properties of the T cells in an abnormal immune system.