This is a competitive renewal of an ongoing project studying dopamine receptors, using positron emission tomography, in chronic schizophrenic patients. To date, we have reported a total of 10 drug-naive schizophrenic patients as having elevated striatal dopamine-2 (D2) receptor densities (Bmax), when compared to age and sex matched controls using C-11-N- Methylspiperone (11CNMSP) PET scanning (Wong, et al, Science, 1986). Farde, et al, using a different ligand and method for assessing dopamine receptor density, were unable to replicate this finding. The work proposed herein consists of three aims. First, we will study drug-naive schizophrenic patients and appropriate controls using both PET methods (ie, that of Wong, et al, and Farde, et al) and ligands (11-C-N-methylspiperone and raclopride) to resolve the controversy over dopamine-2 receptor Bmax estimates in drug-naive schizophrenic brains. Second, we will estimate dopamine-1 (D1) receptor densities (Bmax) using the potent dopamine-1 receptor antagonist, 3H-SCH22390 and D2 density (Bmax) using 11CNMSP in drug-naive schizophrenics and appropriate controls, to assess the role of D1/D2 abnormalities in schizophrenia. Third, estimates of D2 receptor density from aims 1-2 will be added to prior data so that correlations between clinical and D2 density neuropsychologic phenomena can be made. These studies have great potential to elucidate the role of dopamine abnormalities in the pathophysiology of schizophrenia.