The present study employed the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 to investigate the possible importance of NMDA receptor activation for naturally occurring spatial learning in birds by exploiting the navigational ability of homing pigeons (Columba livia). Control pigeons released from two unfamiliar release sites displayed vanishing bearings that were poorly oriented. However, when released a second time from the same sites they displayed improved homeward orientation. The control birds apparently learned something about the spatial relationships of stimuli at the release sites on the first releases and used that information to orient better when released a second time from the same locations. Experimental pigeons given the NMDA receptor antagonist MK-801 (0.10 mg/kg) initially behaved as controls, orienting poorly when released for the first time from the two sites. In contrast to controls, the experimental birds failed to show significant improvement in orientation when released again from the same sites without MK-801. A second experiment revealed no state-dependent learning. Results of a position/color discrimination task showed that the impairments observed did not generalize to associative learning in an operant chamber, and together with field observations were not a result of sensory or motor drug effects. The data indicate that blocking NMDA receptors can disrupt navigational learning in homing pigeons. As such, the results are consistent with the hypothesis that NMDA receptor activation plays an important role in spatial learning in birds.