Serum-antibodies against an organ specific CNS antigen as well as against serotonin and gangliosides (Gm 1) were analysed by ELISA in 34 patients with schizophrenia, ten patients with schizoaffective psychosis and 13 patients with major depressive disorder. Sixty-two patients with various rheumatic disorders and 32 blood donors were included in the study as controls. Sixty-two percent of the 13 patients with major depressive disorder had antibodies to serotonin and 69% to gangliosides, whereas antibody positive sera was only found in 38% of the 34 patients with schizophrenia. The same antibodies were found in only 6% (antibodies to serotonin) and 13% (antibodies to gangliosides) of the 32 blood donors and in a similar frequency in patients with schizoaffective psychosis. Organ specific antibodies to CNS-antigen could not be detected in the psychiatric patient group at any significant level. It is speculated that auto-immune reactions towards a serotonin receptor may be involved in the etiopathogenesis of major depressive disorder.