We have examined protein synthesis in entorhinal cortex following induction of long-term potentiation (LTP) in perforant path-granule cell synapses. The data presented here indicate that there was an increase in [35S]methionine labelling of TCA-precipitated proteins and [35S]methionine labelling of synaptophysin in the ipsilateral entorhinal cortex 40 min after induction of LTP in dentate gyrus. Intraventricular injection of both the NMDA antagonist, D-amino-phosphonovalerate, and the protein synthesis inhibitor, anisomycin reduced protein synthesis though the decrease caused by anisomycin was much more profound. Both agents blocked induction of LTP and the increase in protein synthesis and synaptophysin synthesis which accompanied LTP. These data indicate a close coupling of increased protein synthesis in the entorhinal cortex and expression of LTP in the dentate gyrus. This coupling was further suggested by the absence of an LTP-associated increase in protein synthesis in aged animals, in which LTP was markedly attenuated. The possibility that these changes impact on morphological changes which accompany LTP is discussed.