Haloperidol and bromperidol are antipsychotic drugs that are classified as butyrophenones, a group of compounds that is widely recognized as one of the most important classes of neuroleptic drugs. Previous studies tend to indicate that blood levels of butyrophenones might not be related to clinically interesting responses. In contrast, however, brain levels of these drugs might correlate with neuroleptic activity. We propose to synthesize 18F-haloperidol and 82Br-bromperidol and several derivatives of these compounds and perform tissue distribution studies with these labeled materials by serial sacrifice and external scintigraphy on rats and monkeys. The relationship between brain concentrations and serum levels will be determined, both after acute and chronic administration. The effects of pretreatment with chlorpromazine and lithium carbonate on the tissue distribution profiles of 82Br-bromperidol and 18F-haloperidol will be determined in the rat and monkey. Emphasis will be placed on brain levels of the radiolabeled drugs. The time course of blood and tissue levels, particularly brain levels, of labeled butyrophenones will be mathematically analyzed using linear compartmental models. The contribution of the major metabolite to the levels of radioactivity obtained from external scintigraphy after administration will be determined. This will be accomplished by determining the parameters for distribution of the metabolite after its IV injection. These parameters will be fixed and incorporated into the model for the parent butyrophenone. It will then be possible to determine the parameters for the parent butyrophenone by standard modeling techniques.