In a combined retrospective and prospective study, we tried to define the prevalence of antinuclear antibodies (ANA) and its clinical relevance in neurological patients. Three hundred twenty-seven neurological patients who had ANA determined because of suspicion of connective tissue disease (CTD), were retrospectively studied. Thirty (9.2%) were ANA positive, 20 (66%) of whom had CTD. Of 327 consecutively admitted patients, prospectively studied, 18 (5.5%) were ANA positive, 5 (28%) of whom had evidence of CTD. Systemic lupus erythematosus (SLE) was the most frequently diagnosed CTD. In a prospective study of 48 multiple sclerosis (MS) patients, only 1 had detectable ANA at a dilution of 1:40. Lupus anticoagulant (LA) was prospectively detected in 2 patients but was not associated with a vascular or autoimmune systemic disease.