Dopaminergic modulation of neuronal function has been extensively studied in the prefrontal cortex, but much less is known about its effects on glutamate-mediated synaptic transmission in the entorhinal cortex. The mesocortical dopamine system innervates the superficial layers of the lateral entorhinal cortex and may therefore modulate sensory inputs to this area. In awake rats, systemic administration of the dopamine reuptake inhibitor GBR12909 (10 mg/kg; i.p.) enhanced extracellular dopamine levels in the entorhinal cortex and significantly facilitated fEPSPs in layer II evoked by piriform cortex stimulation. An analysis of the receptor subtypes involved in the facilitation of evoked fEPSPs was conducted using horizontal slices of lateral entorhinal cortex in vitro. The effects of 15-min bath-application of dopamine on synaptic responses were bidirectional and concentration-dependent. Synaptic responses were enhanced by 10 µM dopamine and suppressed by concentrations of 50 and 100 µM. The D₁ receptor antagonist SCH23390 (50 µM) blocked the significant facilitation of synaptic responses induced by 10 µM dopamine, and the D₂ receptor antagonist sulpiride (50 µM) prevented the suppression of fEPSPs observed with higher concentrations of dopamine. We propose here that dopamine release in the lateral entorhinal cortex, acting through D₁ receptors, can lead to an enhancement of the salience of sensory representations carried to this region from adjacent sensory cortices.