In order to determine the prevalence and clinical significance of beta 2-GPI-dependent anticardiolipin antibodies (beta 2-GPI/aCL) in patients with systemic sclerosis (SSc), serum samples from 80 patients with SSc, 20 patients with systemic lupus erythematosus (SLE), and 120 healthy control subjects were examined by ELISA using purified beta 2-GPI. IgG isotype beta 2-GPI/aCL was present in eight of 80 patients with SSc (10%), and the presence of beta 2-GPI/aCL IgG was significantly correlated with the presence of isolated pulmonary hypertension (PH). Furthermore, levels of beta 2-GPI/aCL IgG were significantly correlated with levels of mean pulmonary arterial pressure. These data suggest that IgG isotype beta 2-GPI/aCL might be a serological indicator of the severity of PH in patients with SSc.