Extracellular field recordings were performed in guinea-pig and rat neocortical slice preparations maintained in vitro. Bath application of the convulsant drug 4-aminopyridine (4-AP, 100 microM) induced spontaneous epileptiform potentials in 80% of the guinea-pig neocortical slices and only in 6% of the neocortical slices from rat. In both species spontaneous epileptiform activity consisted of a 4-16 s long ictal-like discharge that recurred with a frequency range of 0.01-0.02 Hz. In rat neocortical slices stimulus-induced responses resembled the spontaneous occurring epileptiform events. Ictal-like discharges in guinea-pig neocortical slices were blocked by the N-methyl-D-aspartate (NMDA) receptor antagonist 3-((+/-)-2-carboxypiperazine-4-yl)propyl-1-phosphonic acid (5 microM), while those in the rat disappeared during perfusion with the non-NMDA excitatory amino acid receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (1-3 microM). These results indicate that the neocortex of guinea-pig has a higher propensity to generate 4-AP-induced spontaneous epileptiform activity than that of rat. Furthermore the epileptiform activity in these two species requires a different involvement of excitatory amino acid receptors.