Microiontophoretically applied adenine nucleotides depressed the firing of corticospinal and other unidentified cerebral cortical neurones. Adenosine 3′,5′-cyclic monophosphate was less potent than the other adenine nucleotides. Guanine nucleotides shared this depressant activity, although they were less potent. Pyrimidine nucleotides and xanthine derivatives were largely devoid of depressant activity. Adenosine triphosphate had an additional excitant action on some neurones, but this effect was not observed with corticospinal cells.