BACKGROUND AND OBJECTIVE: The clinical importance of antiphospholipid antibodies (APA) derives from their association with a syndrome of venous and arterial thrombosis, recurrent fetal loss and thrombocytopenia known as the antiphospholipid syndrome (APS). The Italian Registry of Antiphospholipid Antibodies was set up in 1989 for the purpose of collecting a large number of patients with lupus anticoagulant (LA) or anticardiolipin antibodies (ACA) for clinical studies in order to obtain more information on the clinical features of APS. EVIDENCE AND INFORMATION SOURCES: The Italian Registry has completed two clinical studies and proposed an international trial on the treatment of APS patients. These activities of the Registry are reviewed herein. Additional information has been obtained from pertinent articles and abstracts published in journals covered by the Science Citation Index and Medline. STATE OF ART: The first study of the Registry was a retrospective analysis of enrolled patients which showed that: a) the prevalence of thrombosis and thrombocytopenia was similar in cases with idiopathic APA or APA secondary to systemic lupus erythematosus, and b) the rate of thrombosis was significantly reduced in patients with severe thrombocytopenia but not in those with only a mild reduction of the platelet count. The second study was a prospective survey of the natural history of the disease, showing that a) previous thrombosis and ACA titer > 40 units were independent predictors of subsequent vascular complications; b) a history of miscarriage or thrombosis is significantly associated with adverse pregnancy outcome; c) hematological malignancies can develop during follow-up and patients with APA should be considered at increased risk of developing NHL. Thus the possibility of a hematologic neoplastic disease should be borne in mind in the initial evaluation and during the follow-up of these patients. PERSPECTIVES: The latest initiative of the Registry was the proposal of an international, randomized clinical trial (WAPS study) aimed at assessing the efficacy and safety of high-dose warfarin in preventing recurrent thrombosis in patients with APA and vascular disease. The study is scheduled to start in March 1997.