The effects of behaviorally equivalent doses of D-amphetamine and cocaine on extracellular dopamine (DA) levels in the left and right medial prefrontal cortex (PFC) were investigated using microdialysis in anesthetized rats. The two drugs increased extracellular DA levels to a similar extent and, in each case, there was a tendency for the effects to be greater in the left than in the right side of the brain. For both drugs, there was a strong negative correlation between basal levels and the magnitude of the drug response; this relationship, while important to consider when comparing one drug to another, could not account for the left-right differences in drug effects. Contrary to some previous reports, the present data indicate that D-amphetamine and cocaine do not differ substantially with regard to their effects on dopamine neurotransmission in the PFC.