Synthetic substance P has been discovered to stimulate significantly the formation of dopa in the limbic, striatum, hemisphere and diencephalon regions of the brain and the lower brain stem. There was no effect upon 5-hydroxytryptophan formation or on tryptophan or tyrosine levels. After inhibition of monoamine synthesis by N'-(DL-SERYL)-N2-(2, 3, 4-trihydroxybenzyl)hydrazine, substance P significantly accelerated the disappearance of dopamine, noradrenaline and 5-hydroxytryptamine. Substance P appears to stimulate monoaminergic neurons in the brain and to serve as an excitatory transmitter in nerve terminals impinging upon dopaminergic cell bodies. A similar stimulation of noradrenaline and 5-hydroxytryptamine indicate a similar transmitter role for noradrenergic and serotonergic neurons. These data strengthen questions about the possible clinical influence of substance P in disease states involving monoaminergic mechanisms including Parkinsonism and schizophrenia.