Animal studies: The comparative effects of haloperidol, chlorpromazine, thioridazine and clozapine on dopamine (DA) metabolism in the striatum, tuberculum olfactorium and nucleus accumbens of the rat will be studied utilizing gas-chromatographic techniques recently developed in this laboratory. These methods permit the simultaneous determination of the major DA metabolite 3,4,-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in as little as 1 mg rat striatal tissue, and DA in one-fifth of the striatal tissue of a single rat. The effects of these neuroleptics will be probed in detail in acute and chronic studies. The dynamics of DA metabolism in the meso-limbic dopaminergic system will be compared to that of the striatum by studying the effect of alpha-methyl-p-tyrosine, tropolone, pargyline, and probenecid on DA and its metabolites in these structures. Clinical studies: Collaborative psychopharmacologic studies will be carried out on patients with acute schizophrenia and other psychiatric disorders. These investigations will involve precise gas- chromatographic determination of the levels of the major DA metabolites DOPAC and HVA as well as the major norepinephrine metabolite 3-methoxy- 4-hydroxyphenylethylene glycol (MHPG) in patient cerebrospinal fluid before and after drug therapy. These studies are of particular relevance to the "dopaminergic theory of schizophrenia."