Antiphospholipid antibodies, lupus anticoagulant antibodies to cardiolipin, and a false-positive result on testing for syphilis have been linked to thrombotic vascular occlusions, particularly in patients with systemic lupus erythematosus (SLE) or lupus-like disease, i.e., patients not fulfilling four American Rheumatism Association criteria for the classification of SLE. The clinical and serologic features of 35 patients with cerebrovascular disease (strokes/transient ischemic attacks) who demonstrated antibodies to phospholipids are presented. Complete histories were obtained from all 35 patients, and all underwent routine physical examinations, radiography, electrocardiography, computed tomographic brain scanning, and immunologic studies. Psychometric tests were performed in nine patients. The strokes were often multiple and were followed by multi-infarct dementia in nine patients. Of particular interest were 10 patients in whom the presence of antiphospholipid antibodies was the major and often the sole immunologic disturbance present. Several of these patients were antinuclear antibody-negative, and the antinuclear antibodies, when present, were usually of a low titer (1:40 to 1:160). These patients conform to a group classified as having a primary antiphospholipid syndrome. Antiphospholipid antibodies are strongly associated with cerebrovascular occlusions in patients with SLE as well as in those with lupus-like disease and the primary antiphospholipid syndrome. All patients with any of these conditions who present with vascular events should be screened for these antibodies, as their occurrence may have a bearing on future therapy.