Quantitative determination of IgG and IgM antibodies to cardiolipin (anti-CL) was performed with a newly developed sensitive and specific ELISA method. We studied a cohort of 361 unselected patients with various autoimmune rheumatic diseases (ARD), 69 patients with thromboembolic phenomena (TEP) unassociated with ARD, and 267 healthy blood donors (HBD). Anti-CL of at least one immunoglobulin class were found in 42 (11.6%) of the ARD patients, in 3 (4.3%) of the TEP patients (2 with myocardial infarction and 1 with pulmonary emboli), and in 6 (2.3%) of the HBD. In ARD patients anti-CL were more prevalent in patients with systemic lupus erythematosus (SLE) and overlap syndromes. Significant correlations included CNS involvement (particularly seizures) and features of immune hyperreactivity (splenomegaly-lymphadenopathy, ANA, and antibodies to Ro(SSA), U1-nRNP, and double-stranded DNA). No statistical correlation could be demonstrated between the presence of anti-CL and thrombotic events, hematologic disorders, or recurrent abortions in the ARD patients.