Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disease characterized serologically by B cell hyperactivity and a panoply of autoantibodies against nuclear, cytoplasmic and cell surface antigens. It is thought that T cells are involved in this process and more recently it has been suggested that the CD4' CDS', i.e. double negative (DN) T cells, might be important. As a start to understanding the contribution of DN T cells to disease pathogenesis in SLE, the percentages of DN T cells were determined and it was found that αβ but not γδ DNT cells were significantly increased in patients with SLE when compared to rheumatoid arthritis (RA) (autoimmune controls) and healthy controls. To further establish their participation in the autoimmune reactions in SLE, the activation markers expressed by the DN T cells were examined. It was found that HLA-DR and CD69, and co-stimulatory molecules CD28 and CTLA-4 were all expressed by significantly higher percentages of DNT cells from patients with SLE, than those with RA or healthy controls (HC). More DN T cells from SLE patients were CD45RA+ than from controls, while CD45R0+ were reduced. DN T cells in patients with SLE also showed a more activated phenotype than their CD4+/CD8+ counterparts. To understand the functional significance in SLE DNT cells, the percentages of SLE αβ TCR+ DN T cells containing intracellular IL-4, a Th2 cytokine was determined. Higher percentages of SLE αβ TCR DN+ T cells contained IL-4 constitutively than RA or HC. DN T cell populations from patients with SLE showed greater resistance to apoptosis in culture than the conventional CD4/CD8+ cells and DN T cells from healthy controls. High Bcl-2/Bax ratios and higher levels of Bcl-x observed in the DN T cells from patients with SLE could explain their resistance to apoptosis compared to the conventional T cells and DN T cells from healthy controls.