The medial prefrontal cortex (mPFC) has been associated with diverse functions including attentional processes, visceromotor activity, decision making, goal directed behavior, and working memory. The present report examined the effects of stimulation of the midline thalamus, concentrating on ventral nuclei of the midline thalamus, on evoked activity at the mPFC. The nucleus reuniens (RE) of the ventral midline thalamus is a major source of projections to the hippocampus and to the mPFC, and has been shown to exert pronounced excitatory effects on the hippocampus. No previous study has systematically examined the actions of the ventral midline thalamus on the mPFC. We showed that stimulation of the dorsal and ventral midline thalamus, but not of an intermediate region lying between them (null zone), produced short latency, large amplitude evoked potentials throughout the dorsoventral extent of the medial PFC. The largest effects were elicited with ventral midline stimulation (rhomboid/reuniens nuclei) at the ventral mPFC--the prelimbic (PL) and infralimbic (IL) cortices. Specifically, stimulation of RE produced evoked potentials (early negative component, N2) at the PL cortex at a mean latency of 22.6 msec and mean amplitude of 0.85 mV, indicative of monosynaptic effects. In addition, we showed that paired pulse stimulation of RH/RE produced strong facilitatory actions (paired pulse facilitation) at IL (83%) and PL (75%). These findings indicate that RE exerts strong direct excitatory effects on the mPFC, and coupled with the demonstration that RE produces similar actions on the hippocampus, indicates that RE is in a position to influence and possibly coordinate the activity of these two forebrain structures subserving memory.