1. The hyperactivity and hyperpyrexia produced by L-tryptophan in rats treated with a monoamine oxidase inhibitor was inhibited by chlorpromazine.2. Chlorpromazine did not inhibit the increased rate of synthesis of brain 5-hydroxytryptamine (5-HT) produced by tryptophan loading.3. Hyperactivity and hyperpyrexia were also produced by 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) in rats. Pretreatment with a monoamine oxidase inhibitor potentiated the hyperactivity response. Pretreatment of rats with p-chlorophenylalanine did not inhibit hyperactivity produced by 5-MeODMT.4. Chlorpromazine inhibits hyperactivity caused by tryptophan or 5-MeODMT after monoamine oxidase inhibition either by competition with 5-HT or 5-MeODMT, respectively, at receptor sites or by physiological antagonism.