This study examined [3H]MK-801 binding to the N-methyl-D-aspartate (NMDA) receptor in membranes prepared from cerebral cortex, hippocampus and corpus striatum of 3 week old rats exposed to 10 weeks of intermittent hypobaric hypoxia (4300 m; 450 Ton) and compared results with those of normoxic controls. The cortex, hippocampus and striatum of hypoxic animals had a 36, 35 and 31% reduction in binding sites (B(max)) and a 29, 32 and 17% decrease (reflecting increased affinity) in the dissociation constant (K(d)) when compared to controls. In the cerebral cortex, both glutamate (100 μM) and glycine (10 μM) enhanced [3H]MK-801 binding by two to 3-fold. Coagonist glutamate, however, had a higher EC50 (0.44 μM) in the hypoxic cortical membranes when compared to controls (0.28 μM). No significant differences were found in the EC50 of glycine. The results show that the NMDA receptor is altered in several brain regions of rats developing in a hypoxic environment.