Excitatory amino acids, acting at the N-methyl-d-aspartate (NMDA) receptor, have been postulated to play an important role in the acquisition of behavior (learning). Previous studies have shown that some forms of response acquisition can be impaired by drugs that block the NMDA receptor. To determine whether excitatory amino acid blockade could also affect the ability to acquire an emotional response, the effects of the noncompetitive NMDA receptor antagonist MK-801 were studied on the development of response suppression under a conditioned emotional response (CER) procedure in the rat. The CER procedure progressively suppressed responding when saline was given prior to the eight daily sessions over which animals were initially exposed. Daily treatment with MK-801 blocked the development of response suppression. Thus, these data are consistent with the notion that excitatory amino acid blockade prevents or diminishes the development of a learned emotional response. This suggests a potential role for this receptor in the development of anxiety-related disorders in humans.