Recently, the applicant found that 44% of patients with schizophrenia had serum IgG antibodies to hsp60. of 100 control subjects, anti-hsp60 antibodies were detected in only 8 patients, all of whom had active infectious or immune disease. These findings are important because they imply that an infection or an aberrant immune response may be involved in the pathogenesis of schizophrenia of some patients and also because proteins that are cross-reactive with hsp60 are implicated in the pathogenesis of experimental models of autoimmune arthritis and diabetes. The overall aim of this proposal is to investigate the characterize the association of the anti-hsp60 antibodies with schizophrenia. The specific aims are: a) Does the anti-hsp60 antibody response in schizophrenia have specific clinical associations; b) Is there an intrathecal response to hsp60 in schizophrenia; c) Do antibodies in patients with schizophrenia cross-react with other neural proteins which might be involved in the pathogenesis of the disease; d) Are there abnormalities in the structure or distribution of hsp60 in patients with schizophrenia which might cause the protein to become immunogenic; and e) Do anti-hsp60 antibodies in schizophrenia recognize unique determinants that are shared by hsp60 in other specific organisms which might trigger the disease. The anti-hsp60 antibodies will be measured by Western blotting and radio- immune assay and other studies will involve immunocytochemistry, peptide mapping, gene cloning and epitope mapping.