We describe a patient with systemic lupus erythematosus who, after a disease flare, sequentially produced antibodies to specific Sm polypeptides (demonstrated by counterimmunoelectrophoresis, immunoblotting, and RNA immunoprecipitation) concomitantly with the disappearance of anti-double-stranded DNA antibodies. Immunoblotting studies revealed that antibodies to the D polypeptide appeared first, followed by antibodies to BB' and E polypeptides, respectively. Our findings suggest that antibodies to the Sm-specific polypeptides do not occur simultaneously and that the regulation of their production is independent of that of antibodies to double-stranded DNA.