OBJECTIVE Anticardiolipin antibodies (aCL) are associated with thrombosis in patients with systemic lupus erythematosus (SLE). Our aim was to determine whether there is an association between aCL, anti-Sm antibodies, and thrombosis in patients with SLE. METHODS Sera from 153 patients with SLE were studied by ELISA, immunoblotting, and counter-immunoelectrophoresis (CIE) for anti-Sm antibodies, aCL and anti-dsDNA antibodies were detected by ELISA and radioimmunoassay, respectively. RESULTS Anti-Sm antibodies were detected in 62 patients (40.5%) by ELISA and in 16 (10.4%) by CIE; IgG-anti-BB'-Sm in 44 (28.7%) by immunoblotting; IgG-aCL in 82 (53.5%), IgM-aCL in 44 (28.7%), and anti-dsDNA antibodies in 128 (83.6%). Anti-Sm and anti-dsDNA antibodies were significantly more frequent in patients with than in patients without aCL. Of the 89 patients with aCL, 36 (40.4%) showed IgG-anti-BB'-Sm antibodies (OR: 4.7; 95% CI: 2-10.5). Thrombosis was present in 20 (22.4%) SLE patients with aCL and in two (3.1 %) SLE patients without aCL (OR: 8.9; 95% CI: 2.4-31.8). Of the 22 patients with thrombosis, five (22.7%) had precipitating anti-Sm antibodies (OR: 3.2; 95% CI: 1.04-9.8) and 14 (63.6%) showed IgG-anti-BB'-Sm antibodies (OR: 5.8; 95% CI: 2.3-14). Anti-BB'-Sm and aCL were significantly more frequent in patients with anti-dsDNA antibodies (32 and 62%) than in patients without these antibodies (12 and 36%) (OR: 3.4 and 2.9; 95% CI: 1.03-11.1 and 1.2-6.7, respectively). CONCLUSIONS IgG-anti-BB'-Sm antibodies are associated with aCL, anti-dsDNA, and thrombosis in patients with SLE. Our findings suggest a possible association between anti-Sm, anti-dsDNA, and aCL responses in these patients.