Haloperidol increases the plasma concentration of the dopamine (DA) metabolite homovanillic acid (HVA). Since a substantial proportion of plasma HVA originates outside the brain, this effect could be due to a combination of both peripheral and central actions of haloperidol. In order to evaluate the relative contribution of central versus peripheral effects of haloperidol on plasma HVA, the effect of pretreatment with a peripheral monoamine oxidase inhibitor, debrisoquin, on the plasma HVA response to haloperidol was examined. In addition, the effect of haloperidol on plasma HVA was compared with that of domperidone, a peripheral DA receptor blocking agent. Debrisoquin pretreatment did not alter the haloperidol-induced increase in plasma HVA and domperidone had no effect on plasma HVA. Thus, the haloperidol effect on plasma HVA did not appear to be due to increased peripheral HVA production or blockade of peripheral DA receptor sites. It is concluded that the haloperidol-induced increase in plasma HVA is due largely or exclusively to the drug's action on the brain.