Increased prevalence of autoantibodies has been suggested in patients with epilepsy. This study determined the presence of autoantibodies in a representative cohort of 960 patients with epilepsy. The frequency of antinuclear antibodies (ANA), immunoglobulin G class anticardiolipin antibodies (aCL) and anti-B2-glycoprotein I antibodies were studied in 960 consenting adult patients with epilepsy and in 580 population-based reference subjects identified from the Finnish Population Registry. Overall the frequencies of the autoantibodies studied did not differ between patients with epilepsy and reference subjects. aCL were present in 4.5% of the patients and in 5.0% of the reference subjects and 17% of both the patients and the reference subjects had antinuclear antibodies. However, patients with partial epilepsy for > or =30 years were three times more likely to have aCL than patients with partial epilepsy for <10 years. Patients with partial epilepsy and > or=1 seizure per month were 2.2 times more likely to have aCL than patients with partial epilepsy with <1 seizure per month. Moreover, ANA tended to be more frequent among patients with > or =1 seizure per month. No association was found between the major antiepileptic drugs and autoantibodies. Overall the frequencies of the autoantobodies studied were similar in the large epilepsy cohort and in matched reference subjects from the general population. However, a long duration of epilepsy and poor seizure control were associated with an increased presence of aCL in patients with partial epilepsy.