It has been demonstrated that antiphospholipid antibodies (aPL) recognize epitopes formed by anionic phospholipids and protein cofactors. beta 2 glycoprotein I (beta 2GPI) is accepted as the cofactor of anticardiolipin antibodies (aCL). In the present study we explored the presence and clinical associations of anti beta 2GPI antibodies of IgG isotype (a beta 2GPI-IgG), measured by ELISA. We studied sera from 169 patients with aCL and/or lupus anticoagulant (LA), including 52 patients with systemic lupus erythematosus and 49 with primary antiphospholipid syndrome (PAPS). We found 31.9% positive sera for a beta 2GPI-IgG in the whole population and 48.6% in the aCL-IgG(+) group. There was a good correlation between the titre of aCL-IgG and the optical density for a beta 2GPI-IgG (r = 0.69, P < 0.01). The presence of a beta 2GPI-IgG was associated with the presence of aCL-IgG (P < 0.0001) and LA (P < 0.0005). However, none of 23 LA (+) patients without aCL had a beta 2GPI-IgG. We found a statistically significant association between the presence of a beta 2GPI-IgG and a history of venous thromboembolism (VTE) in our patients (P < 0.005). This association was observed in PAPS (P < 0.05) but not in secondary antiphospholipid syndrome (SAPS). Our study confirms that some aPL(+) sera react with beta 2GPI in special experimental conditions. In addition, the presence of these antibodies is associated with a history of VTE.