Genetically epilepsy prone rats (GEPR) are hypersensitive to various epileptogenic treatments and undergo characteristic generalized seizures when exposed to potent acoustic stimulation. We have studied the sensitivity of GEPR to high atmospheric pressure. Threshold pressures for behavioral symptoms of the high pressure neurological syndrome (HPNS) were recorded in normal Sprague-Dawley (SD) and GEPR (which originate from the SD strain) of both sexes. The threshold pressure (TP) for tremor and for convulsion was significantly lower in GEPR than in SD rats. The protective action of the NMDA receptor antagonist D-2-amino-7-phosphono-heptanoate (D-APH) was tested on both strains of rats. D-APH, 90 mg/kg ip was more protective against tremor in SD than in GEPR. Female GEPR were not protected against tremor. Protection against clonic seizures was similar in both sexes of GEPR and female SD rats while SD males were not significantly protected. None of the animals treated with D-APH developed the tonic phase of seizures. Blockade of the NMDA receptor with D-APH brought the threshold for convulsions in GEPR to a similar pressure to that obtained in SD vehicle-injected controls. This findings suggests the involvement of the excitatory amino acid system in the hypersensitivity of GEPR to high atmospheric pressure.