Ovarian hormones influence memory formation by eliciting changes in neural activity. The effects of various concentrations of progesterone (P4) on synaptic transmission and plasticity associated with long-term potentiation (LTP) and long-term depression (LTD) were studied using in vitro hippocampal slices. Extracellular studies show that the highest concentration of P4 tested (10[superscript -6] M) decreased the baseline synaptic transmission and magnitude of LTP, but did not affect LTD. Intracellular studies suggest the P4 effect to be mediated, at least in part, by GABA[subscript A] activity. These results establish a general effect of P4 on synaptic transmission, multiple forms of synaptic plasticity, and a possible mechanism of P4 action in hippocampus.