Hypoxia is the most common cause of neonatal seizures and encephalopathy. We have previously developed an in vivo experimental model of perinatal hypoxia which exhibits age-dependent acute and chronic epileptogenic effects. Between postnatal day (P) 10-12, the rat exhibits acute seizure activity during global hypoxia, while no seizures are induced at earlier (P5) or older (P60) ages. Rats exposed to hypoxia between P10-12 have reduced seizure thresholds to chemical convulsants in adulthood. The nonNMDA antagonists NBQX appears to suppress both the acute and long term epileptogenic effects of hypoxia. The age-dependency of the hyperexcitable response to hypoxia in vivo can be reproduced in vitro using hippocampal slices. In Mg(2+)-free media, hypoxia induced ictal discharges within 60 s of onset in 79% of slices from normal P10 rat pups compared to 11% of adult slices (p < 0.001). Model systems such as that described here allow for correlation of in vitro and in vivo electrophysiology and should provide data regarding the pharmacological and physiological characteristics of hypoxia-induced seizure activity in the immature brain which could ultimately be applied to therapeutic strategies.