Free Sm was purified by gel filtration and anti-Sm affinity chromatography. Using this purified antigen, an ELISA for anti-Sm was performed. Three hundred and fifty patients with various rheumatic diseases were studied with respect to immunoglobulin classes of anti-Sm by ELISA. A high frequency of IgG anti-Sm was specifically detected in patients with systemic lupus erythematosus (SLE), but IgA and IgM anti-Sm showed a low frequency and also was detected in other diseases. In patients with SLE, anti-Sm significantly correlated with lung fibrosis and pericarditis. In our longitudinal study, there were increases in titer of IgG anti-Sm preceding central nervous system exacerbation and serositis. IgG anti-Sm was found to be not only a diagnostic marker but also a reliable measure of disease activity in SLE.