Antibodies to the SS-B (La) nuclear ribonucleoprotein particle are relatively specific for the diagnoses of Sjögren's syndrome or systemic lupus erythematosus. The formation of such autoantibodies is likely, then, to reflect the basic immunopathogenesis of these disorders. We have studied the isotype distribution of anti-SS-B antibodies as a clue to their immunoregulation. Using specific ELISA assays, we found that nearly all anti-SS-B antibodies in 39 patients were IgG, and, of these, only the IgG1 and, to a much lesser extent, IgG3 subclasses were represented. Both kappa and lambda light chain antibodies were found in most sera, and the overall kappa/lambda ratio approximated that of normal serum immunoglobulin. These results suggest that the formation of anti-SS-B antibodies is T-cell dependent and that the response is polyclonal in most patients.