The contextual specificity of appetitive conditioned responding was examined in rats undergoing chronic intracerebroventricular infusion of 15 or 30 mM D-2-amino-5-phosphonopentanoic acid (D-AP5) or with excitotoxic hippocampal lesions. The magnitude of conditioned responding by control rats and rats infused with D-AP5 to a conditioned stimulus (CS) trained in Context A was attenuated when the same stimulus was presented in Context B. By contrast, hippocampal-lesioned rats displayed comparable levels of responding to the CS when presented in either Context A or B. Subsequent in vivo electrophysiological investigations showed that the D-AP5 concentrations were effective in blocking long-term potentiation (LTP) in the dentate gyrus. Results indicate that rats are capable of processing contextual information in the absence of N-methyl-D-aspartate (NMDA) receptor-dependent LTP and demonstrate an important dissociation between the effects of hippocampal lesions and the blockade of NMDA receptors in the hippocampus.