This study was carried out to clarify the frequency of detection of antibody activity to ribosomal protein S10 (anti-S10) in patients with systemic lupus erythematosus (SLE) with anti-Sm antibodies (anti-Sm), and clinical differences between anti-Sm-positive SLE patients with and without anti-S10. Twenty-seven of 31 serum samples containing anti-Sm reacted with ribosomal protein S10 along with Sm core proteins B/B' and D (87.1%). Four serum samples containing anti-Sm against only B/B' but not D did not react with S10 (12.9%). Patients who had both anti-Sm and anti-S10 showed lower serum complements levels, high frequency of skin lesion and anti-double-stranded DNA antibody. Many anti-Sm antibodies may recognize B/B', D, and S10 simultaneously, and such antibodies may appear in active disease.