The effects of indolealkylamine and phenylethylamine psychotomimetic drugs on brain 5-hydroxytryptamine (5-HT) metabolism have been studied. Indolealkylamines (psilocybin, psilocin, _.N-dimethyltryptamine or DMT) have a lysergic acid ' diethylamide (LSD)-like effect (increased 5-HT with concomitant decrease in 5-hydroxyindoleacetic acid, 5-HIAA). A degree of inhibition of monoamine oxidase can be demonstrated with psilocybin and psilocin, but not with LSD. The data suggest that other factors are operative in producing decreased levels of 5-HIAA. Phenylethylamines (mescaline, 2,5-dimethoxy-a,4-dimethylphenylethylamine or DOM) not only increase 5- HT but also, at higher doses, 5-HIAA; at lower doses, there is some indication of an LSD-like effect on 5-HIAA. Both categories of drug influence 5-HT metabolism, and the noted differences with respect to 5-HIAA cannot as yet be accounted for.