This paper describes some functional and pharmacological properties of GABA-mediated mechanisms in the human neocortex maintained in vitro in a slice preparation. Neocortical neurons recorded intracellularly under normal conditions generate stimulus-induced and spontaneous potentials that are mediated by the activation of postsynaptic GABAA and GABAB receptor subtypes. As reported in other species, pharmacological blockade of the GABAA receptor makes epileptiform bursts appear in response to extracellular focal stimuli, thus indicating that inhibition mediated through the activation of the GABAA receptor exerts an important role in controlling neuronal excitability in the human neocortex. Spontaneous, prolonged epileptiform discharge are recorded when slices are bathed in Mg(2+)-free medium. Under these experimental conditions GABAA receptor mediated potentials occur between epileptiform events; moreover their rate of occurrence decreases shortly before the onset of each discharge. Blockade of GABAA receptor mediated potentials during application of Mg(2+)-free medium (i) prolongs the epileptiform discharges, (ii) increases the amplitude of their field potential DC shifts, and (iii) augments the concomitant decreases in [Ca2+]0 and increases in [K+]0. These findings indicate therefore that GABAA receptor mediated inhibitory potentials are operant during Mg(2+)-free epileptiform activity, and modulate the occurrence of epileptiform discharges. Moreover, they may also play a role in controlling the changes in [Ca2+]0 and [K+]0 that accompany each epileptiform event.