Seizure susceptibility waxes and wanes in an apparently circadian manner in many epileptic patients. Fluctuations of melatonin concentration with highest levels during the night and lowest levels in the early morning could be involved in this phenomenon. Therefore, the action of melatonin on epileptic activity was tested. The experiments were carried out on human temporal neocortical slices cut from tissue resected for surgical treatment of epilepsy. Autoradiographic studies were performed on parallel slices with 100-120 pmol 2-[125I]iodomelatonin/l in the absence or presence of unlabelled melatonin. High-affinity binding sites of melatonin could be demonstrated in layers II-V of the temporal cortex. The binding was saturable, specific and occurred with low capacity. In electrophysiological studies, epileptiform field potentials were elicited by omission of Mg2+ from the superfusate and recorded from layers II-V. The frequency of occurrence of epileptiform field potentials was reduced to 0.5 of the initial value with application of melatonin (10 and 100 nmol/l) in each case. This effect was reversible upon washing. The findings favour the hypothesis that melatonin depresses epileptiform neuronal activity through specific neocortical receptors.