Despite the concentration of effort in recent years, the mechanisms underlying the expression of long-term potentiation (LTP) in the hippocampus remain elusive, but amidst the uncertainty and sometimes controversy, one consistent finding is emerging; this is that late-phase LTP requires synthesis of proteins. This hypothesis was first proposed by a number of groups who reported that the more persistent components of LTP were blocked by protein synthesis inhibitors, and was supported by a significant literature which indicated that morphological changes accompanied LTP. Recent evidence indicated that the increase in protein synthesis may be cAMP-dependent and that subsequent activation of the transcription factor, CREB, represented one step in the cascade of events leading to protein synthesis. Whether protein synthesis occurs in presynaptic or postsynaptic neurons, or both, is still a subject of debate. Here we present evidence which suggests that LTP in perforant path-granule cell synapses is accompanied by protein synthesis, specifically synthesis of synaptic vesicle proteins, in the entorhinal cortex. We also show that protein synthesis is decreased in the entorhinal cortex of aged rats and a strain of rat which is genetically hypertensive, both of which exhibited impaired LTP. We propose that that the observed increase in protein synthesis in the entorhinal cortex, which accompanied LTP in the dentate gyrus, contributes to the reported changes in morphology in the presynaptic terminal.