Two experiments assessed the behavioral effects of dopamine depletions in the medial prefrontal cortex that were produced by injection of the neurotoxic agent 6-hydroxydopamine. In the first experiment, rats were trained to respond on a differential reinforcement of low rates of responding-30 second (DRL30) schedule. On this schedule, rats were only reinforced if they withheld responding for 30 s. Rats with prefrontal dopamine depletions were found to be impaired in the DRL task. These animals responded more than controls, received fewer reinforcers, and were less efficient in their responses. Moreover, an analysis of interresponse times (IRTs) revealed that rats with medial prefrontal dopamine depletions made more responses with short-duration IRTs, and fewer responses with long-duration IRTs. In the second experiment, rats were tested on open field activity, amphetamine-induced locomotor activity and stereotypy. No increase in spontaneous locomotor activity was found following surgery; however, increases in amphetamine-induced locomotor activity and stereotypy were observed. These results are consistent with hypothesized role for the prefrontal cortex in behavioral inhibition, and indicates that prefrontal cortical dopamine is an integral part of the system.