1. Administration of serotonin 5-HT2 receptor antagonists increases the basal release of dopamine in the mesocorticolimbic pathway. 2. Treatment with dopamine D2 receptor antagonists increases impulse-dependent basal dopamine release in the nigrostriatal pathway. D2 antagonists also potentiate carrier-mediated increases in DA efflux from this pathway. 3. The present study compared the effects of a 5-HT2A/C antagonist (ritanserin) and a D2 antagonist (haloperidol) on carrier-mediated (amphetamine-induced) DA release in the mesocortical system. 4. In vivo microdialysis was used to recover extracellular fluid from the medial prefrontal cortex of conscious rats. Samples were then assayed for dopamine content by HPLC with electrochemical detection. Haloperidol or ritanserin were administered systemically (i.p.) 30 min before d-amphetamine (5.0 mg/kg i.p.). 5. Results demonstrated that 5.0 mg/kg ritanserin, but not 1.0 mg/kg, potentiated amphetamine-induced DA release in the prefrontal cortex. Similar to previous findings in the striatum, haloperidol (1.0 mg/kg) also augmented amphetamine-stimulated DA efflux in the cortex. 6. These results suggest that 5-HT2 and D2 receptor antagonists increase impulse-mediated dopamine release in the rat prefrontal cortex which in turn potentiates carrier-mediated release.