The hallmark of autoimmune disease is the production of antibodies to self antigens and presence of activated lymphoid cells at the site of inflammation. Systemic lupus erythematosus (SLE) is characterized by the activation of B- and T-lymphocytes and the production of multiple autoantibodies. The hyperactive B- and T-cells play a major role in the pathogenicity of this disease. We have examined the expression of ets family of genes in peripheral blood mononuclear cells (PBMC) from lupus (SLE), rheumatoid arthritis, scleroderma and Sjogren's syndrome. Both ERGB and ETS2 mRNA were expressed at higher levels in PBMC from SLE patients than healthy individuals. More significantly, ERGB gene expression was high in SLE patients with active disease. The role of ERGB gene products in T-cell activation is being pursued by expressing sense and antisense ERGB cDNA and variant forms of ERGB proteins in T- cells. Molecular markers associated with autoimmune phenotype are being characterized using hematopoietic stem cells derived from normal and autoimmune prone mice.