Schizophrenia is a complex mental disorder. Several genetic abnormalities have been identified in individuals with schizophrenia. The present investigation was undertaken to detect novel schizophrenia-related genes in the brain. Complementary DNA (cDNA) microarray technique was used to identify differentially expressed genes in human postmortem brain samples obtained from individuals who had been diagnosed with schizophrenia and matched normals. Compared to hippocampus from normal brains, hippocampus from schizophrenic brains had seventy-four upregulated genes/expressed sequence tags (ESTs) and eighty-seven downregulated genes/ESTs. In the prefrontal cortical region of schizophrenic brains, nineteen genes/ESTs were upregulated, and twenty genes/ESTs were downregulated. Altered genes belonged to several different gene families such as cancer, cell cycle, hematological and infectious diseases. One significantly upregulated gene (HCLS1 associated protein X-1, HAX1) and one significantly downregulated gene (adiponectin receptor2, AdipoR2) were selected for further investigation in an independent set of postmortem schizophrenic and normal temporal cortical samples, using Western blot analyses. Compared to normal brain samples, HAX1 protein levels were higher, and AdipoR2 protein levels were lower in schizophrenic brain samples. We have identified two novel dysregulated schizophrenia-related genes in postmortem human brain – one downregulated gene adiponectin receptor 2 (AdipoR2), and one upregulated gene HCLS1 associated protein X-1 (HAX1). HAX1 and AdipoR2 have not been previously reported to be dysregulated in schizophrenia. Future studies will investigate the role of these genes in the pathophysiology of schizophrenia.