Higher titers of autoantibodies have been reported in recent studies of depressed patients. In an attempt to investigate the presence of antiphospholipid autoantibodies in patients with depression, sera from both patients and healthy controls were tested for immunoglobulin G and M anticardiolipin and antiphosphatidylserine autoantibodies. We tested positive sera for antiphosphatidylserine (APSA) and anticardi- olipin autoantibody (ACA) in 10 dysthymic, 19 major depressive, and 20 healthy subjects. Tests for ACA-IgM were found to be positive in 1 of the dysthymic patients, in 1 of the major depressives and 1 member of the control group. Positive ACA-IgG was found in 1 of the dysthymic patients, 1 of the major depressives and 1 member of the control group. Positive APSA-IgM was found in 3 of the dysthymic patients, 3 of the major depressives and 4 members of the control group. Positive APSA-IgG was found in 2 of the dysthymic patients, 2 of the major depressives and 3 members of the control group. There were no significant differences in IgG, IgM-ACA and APSA between the dysthymic and major depressive groups and the control group. After categorizing both groups for age and sex, no difference was found in the frequency of ACA and APSA positive sera between both groups, indicating that on the basis of serology, no evidence exists that antiphospholipid autoantibodies might be the etiological factor for dysthymic or major depressive disorders.