In area 17 of the awake macaque, disinhibition by blockade of GABA(A) receptors results in a marked elevation in neuronal excitability, with a particular focus in the supragranular laminae. We examined the possibility that the excitatory supragranular response is N-methyl-D-aspartate (NMDA)-mediated. Laminar activity profiles consisting of flash-evoked field potential, current source density (CSD) and multiunit activity (MUA) measures were obtained during striate cortex penetrations using multicontact electrodes that incorporated single or double microinjection cannulae. Profiles were recorded before and at successive time points after bicuculline induction of disinhibition. Both the noncompetitive NMDA antagonist MK-801 and the competitive antagonist APV reversed bicuculline effects, producing a normal laminar activity profile. NMDA-mediated enhancement of excitatory responses in the supragranular laminae of neocortex is believed to play a role in normal signal processing, as well as in epileptic manifestations.