The prefrontal cortex receives multiple inputs from the hippocampal complex, which are thought to drive memory-guided behavior. Moreover, dysfunctions of both regions have been repeatedly associated with several psychiatric disorders. Therefore, understanding the interconnections and modulatory interactions between these regions is essential in evaluating their role in behavior and pathology. The effects of entorhinal cortex (EC) stimulation on the activity of identified medial prefrontal cortex (mPFC) pyramidal neurons were examined using single-unit extracellular recordings and sharp-electrode intracellular recordings in anesthetized rats. Single-pulse electrical stimulation of EC induced a powerful inhibition in the majority of mPFC neurons examined during extracellular recording. Intracellular recording showed that EC stimulation evoked a complex synaptic response, in which the greater proportion of neurons exhibited excitatory postsynaptic events and/or a short lasting and a prolonged inhibitory postsynaptic response. Furthermore, stimulation of EC selectively produced an augmentation of the bistable up-down state only in the type 2 regular spiking neurons and in a subclass of nonintrinsic bursting neurons. Taken together, these data suggest that the potent inhibition observed following EC stimulation may mask a direct excitatory response within the mPFC which markedly potentiates the bistable states in a select subpopulation of mPFC pyramidal neurons.