Autoimmune sera from patients with systemic lupus erythematosus, scleroderma, or both disorders reactive with the (U1)RNP and Sm antigens were analyzed according to their IgG- and IgM-autoantibody profiles by immunoblotting with HeLa nuclear extracts. Anti-(U1)RNP-specific autoantibodies directed against the 68-kDa polypeptide were found to be predominantly of the IgG type, whereas for the other (U1)RNP-specific protein, 33 kDa, a concomitant occurrence of IgG and IgM class autoantibodies was observed for most patients. In contrast, Sm-specific anti-29/28-kDa autoantibodies were found to be more frequently of the IgM than of the IgG type, while Sm-specific anti-16-kDa antibodies of both classes were present simultaneously in most sera. Of the serum collection reported here only one (U1)RNP-specific serum has been found which lacks anti-Sm antibodies of either class. In general, preclassification of sera by immunodiffusion and counterimmunoelectrophoresis corresponds to the IgG but not to the IgM profile as determined by immunoblotting.