An antiphospholipid antibody (APLA) syndrome has been proposed for those patients with systemic lupus erythematosus (SLE) or with other connective tissue diseases who have APLA and manifestations that seem related to their effect (venous thrombosis, arterial occlusions, thrombocytopenia, hemolytic anemia, recurrent fetal loss, leg ulcers, and livedo reticularis). Occurrence of a primary antiphospholipid syndrome has also been mentioned but not defined. We present 9 young patients who had at least 2 of the clinical manifestations that have been related to high titers of APLA, but had neither SLE nor other recognizable connective tissue disease. We propose criteria for diagnosis of such a primary antiphospholipid syndrome and discuss the possible mechanisms whereby a single autoantibody can cause systemic disease.