Acute administration of methamphetamine produced a dose-dependent depression of tryptophan hydroxylase (TPH) activity. The depression was observed in several serotonergic nerve terminal regions of the rat brain and spinal cord. Complete recovery of TPH activity following methamphetamine treatment occurred in all regions, but the time to recovery varied with the dose administered. In contrast to TPH, tyrosine hydroxylase (TH) was not affected by a single injection of methamphetamine. The data are discussed in the context of the effects of single versus repeated doses of methamphetamine on tryptophan and tyrosine hydroxylase.