Several in vitro studies have demonstrated a polyclonal B cell response to antigenic stimulation in patients with systemic lupus erythematosus (SLE). To determine if this polyclonal response occurs in vivo, 18 patients with SLE were antigenically stimulated with the pneumococcal vaccine Pneumovax . Mean antibody response to immunization was the same in SLE and normal control subjects. Although elevated antibody levels to several viruses were present in SLE subjects preimmunization, these levels did not change postimmunization. Total immunoglobulin levels, immune complex levels, and antiblood group B antibody levels did not change in SLE patients after immunization. Antiblood group A titers rose in both SLE patients and normals due to a media contaminant in the Pneumovax . Thus, SLE patients appear to have a specific antibody response to antigenic stimulation with pneumococcal polysaccharide. Polyclonal activation as seen in vitro in SLE may be more restricted in vivo.