We investigated the production of autoantibodies in severe combined immunodeficient (scid) mice that received an intraperitoneal injection of peripheral blood mononuclear cells (PBMC) from patients with systemic lupus erythematosus. Mice receiving 50 x 10(6) cells consistently engrafted, as evidenced by the presence of human immunoglobulin in the hu-PBL-scid serum; though none, any one, or a combination of the autoantibody specificities found in the donor could be found in the hu-PBL-scid serum. Production of anti-Ro antibody in the hu-PBL-scid chimeric mice could be enhanced by treatment with the Ro antigen. These results indicate that not only can scid mice engrafted with PBMC from patients with SLE produce autoantibody, but also that this production can be manipulated with specific antigen.