The presence of antibodies to cardiolipin (ACL Abs) has been reported in some patients suffering from multiple sclerosis (MS), especially of the "neuromyelitic" type. In addition, bright T2-imaging foci (unidentified bright objects) are occasionally detected on brain magnetic resonance imaging (MRI) scans, in patients with antiphospholipid syndrome. From a cohort of 100 patients with a probable or definite diagnosis of MS according to Poser's criteria, we isolated a subgroup of 20 patients (8 males and 12 females) consistently positive for ACL Abs. These patients were followed up neurologically for 1 to 3 years and brain MRI scanning and a complete autoimmune screening were performed. Nineteen (19 of 20) of our patients had the classic neuroimaging features of MS (multiple white-matter T2 bright foci on the MRI scan). The most common neurological syndrome was chronic, slowly progressing myelopathy (presenting as myelopathy, neuromyelitis optica, or spinocerebellar syndrome; 15 of 20), and optic neuropathy (6 of 20). Headache was a dominant symptom in 8 of 20 patients. Less common symptoms included cognitive and psychiatric disorders and chronic fatigue. The mean levels of ACL Abs were 38.8+/-28.2 GPL (normal values up to 7.5). Oligoclonal bands in the cerebrospinal fluid were detected in only 3 of 20 patients. Patients were treated with acetylsalycilic acid and occasionally with short courses of steroids. The progression of the chronic myelopathic/spinocerebellar syndrome was slower than expected in MS (only 2 patients deteriorated whereas 4 improved during a mean follow-up period of 20.8+/-7.1 months). We conclude that patients with probable or definite diagnosis of MS, and consistently elevated levels of ACL Abs show a slower progression and some atypical (for MS) features, such as persistent headaches and absence of oligoclonal bands in the cerebrospinal fluid. In these patients, other, presumably vascular, mechanisms may be involved in the pathogenesis of the neurological symptoms. Therefore, management should include antiplatelet or even anticoagulant agents.