Sera from patients with systemic lupus erythematosus frequently contain IgM antibodies to glycoproteins of Mr 46,000 and approximately 200,000 isolated from nonionic detergent lysates of mature T cells by affinity chromatography with solid-phase wheat germ agglutinin. Autoantibodies of this specificity correlate strongly with the presence of IgM anti-T cell autoantibodies, as determined by independent indirect immunofluorescence and complement-dependent microcytotoxicity assays, and are specifically absorbed by incubation of patient serum with viable T cells. Collectively, the data suggest that gp46 and, to a lesser extent, gp approximately 200 represent major targets of IgM antilymphocyte autoantibodies in systemic lupus erythematosus.