Substances with varying structural components have been shown to have 5-hydroxytryptamine (5-HT)-like properties in the CNS. In this study, putative 5-HT agonists with indoleamine moeities--lysergic acid diethylamide (LSD) and 5-methoxy-N,N-dimethyltryptamine (5-MeODMT)--and with piperazine moieties--quipazine (Quip) and 6-chloro-2-(1-piperazinyl)pyrazine (6-CPP) were administered to rats. Local cerebral glucose utilisation was measured using the [14C]2-deoxyglucose autoradiographic technique. It was found that in most cerebral structures, these substances produced dose-dependent reductions in glucose utilisation. However, Quip and 6-CPP increased glucose utilisation in specific areas of the diencephalon (e.g., nucleus reuniens) and produced a biphasic effect in some but not all extrapyramidal structures (e.g., ventromedial caudate nucleus). No such increases in local cerebral glucose utilisation were measured following LSD or 5-MeODMT administration. These results indicate that although similarities exist between the effects of indoleamine- and piperazine-containing 5-HT agonists on local cerebral glucose utilisation there are also significant differences in the overall patterns of response produced.