PURPOSE: To determine the frequency of anticardiolipin antibodies (aCL) and their clinical sequelae in family members of aCL-positive patients. PATIENTS AND METHODS: A prospective serologic and clinical evaluation was performed on 23 patients with elevated aCL titers, 87 blood relatives, 18 spouses, and 37 controls. aCL and antinuclear antibodies (ANA) were measured and clinical histories were assessed for all probands, relatives, spouses, and controls. RESULTS: Fifty of 87 relatives screened (57%) had evidence of autoantibody production (aCL and/or ANA). Twenty-nine (33%) had positive aCL titers. Twenty were positive for aCL-immunoglobulin (Ig) G, 7 had evidence of both aCL-lgG and aCL-IgM, and an additional 2 were positive for aCL-IgM alone: In contrast, only 1 spouse was aCL-lgG positive. Thirty-two relatives and 1 spouse were ANA positive. All controls were negative for aCL and ANA. Significant differences were noted between relatives and spouses for aCL-lgG (P <0.00001) and aCL-IgM titers (P <0.0066), and also between relatives and controls (P <0.00001 for both). Clinically, 4 cases of systemic lupus erythematosus (SLE), 4 SLE-like diseases, and 8 aCL-associated illnesses (2 premature strokes, 3 recurrent fetal losses, 1 recurrent thrombosis, and 2 cases of thrombocytopenia) were documented in the relatives. All cases were associated with aCL and/or ANA production. CONCLUSIONS: ANA, aCL, and clinical events associated with antiphospholipid antibodies occur with increased frequency in relatives, but not spouses of aCL-positive probands. These results suggest that aCL-related illnesses may be familial.