A number of derivatives of tryptamine and phenethylamine, and certain other compounds, were tested on neurones in the cerebral cortex of cats by iontophoretic release from micro-pipettes. The characteristic action of many of these compounds was a depression of the neuronal discharge initiated by synaptic activity or by the application of L-glutamate; imidazolylacetic acid, dopamine, ephedrine and ergometrine were particularly effective. Catechol amines, hydroxytryptamines and imidazolylacetic acid had a relatively quick and rapidly reversible action, not unlike that of y-aminobutyric acid, whereas ephedrine and derivatives of lysergic acid diethylamide caused a slower and more prolonged depression of the amplitude of spikes, rather like atropine. Several compounds, including 5-hydroxytryptamine, adrenaline and ergometrine, could also excite the same neurone when larger amounts were applied. A few substances, such as dopa and methylergometrine, had a predominantly excitant action.There has been much speculation during the course of the last decade concerning the significance of several indole and catechol amines which occur naturally in the brain. Interest in these substances has increased as a result of recent developments in the study of psychotropic compounds, some of which are structurally related to the indole and catechol amines (lysergic acid diethylamide, bufotenine, mescaline and others).Evaluation of the importance of these compounds in central nervous mechanisms (Marrazzi & Hart, 1955;Marrazzi, 1957). These findings were substantiated by Ochs, Booker & Aprison (1960), who showed that 5-hydroxytryptamine, applied topically, depressed cortical responses to direct stimulation;