The objective of this study was to define immunologic T cell abnormality characteristic of active systemic lupus erythematosus (SLE). Eight of nine patients who had severe clinical and laboratory manifestations of active SLE had a characteristically marked increase in OKT4+ and a decrease in OKT8+ T cells. Using OKIa1 and OKDR monoclonal antibody, we found that, in circulating blood of all patients with active SLE, an increased percentage of Ia+ and DR+ T cells is present compared to inactive SLE. Five of these active SLE patients had Tac+ antigens, an interleukin 2 receptor on OKT4+ and OKT8+ T cell subsets in resting blood. The present study demonstrates that Ia+ and DR+ antigens are selectively expressed on the majority of OKT4+ T cell subsets of all patients with active SLE, whereas Ia+ and DR+ antigens are expressed almost equally on both OKT4+ and OKT8+ T cell subsets in inactive SLE. The elevated percentage of Ia+, DR+, OKT4+ T cells in active SLE was accompanied by a highly depressed proliferative response to T cell mitogens, phytohemagglutinin and concanavalin A. However, OKT8+ T cell subsets in active SLE possessed a normal proliferative response to these T cell mitogens. We conclude that this abnormality of activated OKT4+ T cells bearing HLA-DR antigens may play a role in the development of active SLE.