The effect of microiontophoretic application of GABA and its antagonist, picrotoxin, on the firing of neurons in the feline caudate nucleus (CN) was studied. Firing was elicited by stimulation of the CN a few millimeters from the recording site. Increasing ejection currents of GABA produced a dose-dependent decrease and eventual blockade of the firing of CN neurons. The GABA current which reduced firing by 50% (ED50) was 7 nA. The Hill coefficient for the action of GABA was calculated as 1.8, indicating that a minimum of two independent subunits of the GABA receptor might need to be simultaneously occupied to activate the conductance change which produces the depressant effect. Picrotoxin blocked the action of GABA in a manner suggestive of a competitive antagonism. Dose ratios for the effects of GABA alone and of GABA during picrotoxin iontophoresis showed the dissociation constant (KD) of picrotoxin for the GABA receptor in the CN to be approximately 5 microM. Our results agree with those reported for different parts of the nervous system in various species, suggesting that the receptor which mediates the depressant effect of GABA in the CN has properties similar to striatal GABA receptors characterized in in vitro studies.