Local changes in extracellular ion concentrations were measured with ion-sensitive microelectrodes in slices of mature (>40 days of age) or immature (16-30 days of age) rat neocortex maintained in vitro. Repetitive stimulation resulted in increases in extracellular potassium ([K+]o) to levels of 8.85 ± 2.1 mM in slices from adult animals and 12.77 ± 1.8 mM in slices from immature animals. During exposure to picrotoxin, maximum levels were 11.3 ± 2.6 and 14.8 ± 2.5 mM in the mature and immature groups, respectively. Picrotoxin (50 μM) induced spontaneous bursts of repetitive spiking, followed by a slow, negative field potential, associated with spreading depression (SD), in slices from immature animals. [K+]o levels increased to 10.2 ± 3.9 mM during repetitive spike discharges and reached 30.3 ± 18.5 mM during SDs. Variations in the size of the extracellular space (ES) were examined during SD. The ES was found to reversibly decrease by 39 ± 4.5%. Clusters of repetitive spikes were associated with 0.1-0.2 mM decreases in [Ca2+]o, whereas 1.12 ± 0.06 mM decreases were observed during SDs. Decreases in [Na+]o and [Cl-o of 56 ± 10 mM and 41 ± 9 mM, respectively, were observed during SDs suggesting that a net transmembrane movement of water occurred during SDs. These results indicate that changes in [K+]o associated with epileptiform activity in the immature nervous system are quantitatively different from those observed in the mature brain. These large increases in [K+]o may contribute to the prolonged nature of epileptiform discharges in the developing nervous system. © 1989.