Antiphospholipid antibodies (aPL) have been reported in the cerebrospinal fluids (CSF) of neurology patients but no CSF studies with psychiatric patients exist. We tested serum from 100 hospitalized psychotic patients having hallucinations and/or delusions for aPL. Patients with positive serum aPL findings were asked to submit CSF for aPL testing. Five CSF samples had aPL specificities not found in the patient's serum suggesting the possibility of intrathecal synthesis. Specificity and isotype discordance between CSF and blood aPL in these psychiatric patients implicates a central nervous system independent autoimmune process that may have an underlying association with the pathophysiology of their diseases.