Previous studies have shown that the number of dendritic spines and synapses in hippocampal CA1 stratum radiatum decreases more than 30% between the proestrus (high estrogen) and estrus (low estrogen) phases of the rat estrous cycle [10,27]. In the present study, we investigated whether hippocampal synaptic plasticity, as measured by long-term potentiation (LTP), might also vary across the estrous cycle of the female rat. Male rats, and female rats at each phase of the estrous cycle were tested in either the morning or afternoon. There were no significant group differences in the pre-LTP I/O curves. However, females examined during the afternoon of proestrus, the phase during which prior studies indicate synapse number to be highest, demonstrated the greatest degree of potentiation. Diestrus, proestrus and estrus females tested in the morning demonstrated similar amounts of potentiation. There were also significant differences in post-LTP I/O curves between the afternoon proestrus females and males tested in the afternoon. These results suggest that gonadal hormones, interacting with the time of day, may regulate neural processes underlying learning and memory.