The expression of dopamine D3-subtype-receptor mRNA was analyzed in defined anatomic regions of brain obtained postmortem from patients with chronic schizophrenia and from controls. The specific amplification of D3-encoding cDNA by PCR allowed the identification of D3 mRNA expression in a wide variety of anatomic regions in both control brains and brains obtained from schizophrenic patients. However, in the parietal cortex (Brodmann areas 1, 2, 3, and 5) and motor cortex (Brodmann area 4), a selective loss of D3 mRNA expression was found in schizophrenia. A different D3 mRNA species was identified that appears to be widely expressed and that is still found in those regions of schizophrenic brains where D3 mRNA could not be detected. Compared with D3 mRNA this RNA is significantly less abundant, and at present its function (if any) is unclear. Many variables associated with either the course and/or the therapeutic management of the disease may account for the selective loss of D3 mRNA in the motor, somatosensory, and somatosensory association areas of schizophrenic brains.