This study tested the role of dopamine receptors in the medial prefrontal cortex (mPFC) in the onset, maintenance, and termination of ethanol and sucrose-reinforced responding. Two groups of Long Evans rats were trained to lever press on a fixed-ratio 4 schedule of reinforcement with 10% ethanol (n = 10) or 5% sucrose (n = 5) presented as the reinforcer. After implantation of injector guide cannulae, the D2/3 agonist quinpirole and the D2 antagonist raclopride were administered bilaterally into the mPFC before behavioral sessions. During control conditions, sucrose reinforcement maintained a 2-fold greater number of responses per session than did ethanol reinforcement. Quinpirole (10.0 micrograms/microliter) reduced total ethanol-reinforced responses by delaying response onset and decreasing the duration of responding, but had no effect on response maintenance (i.e., response rate). A higher dose of quinpirole (20.0 micrograms/microliter) decreased total sucrose responses by simultaneously decreasing duration and response rate, without altering response latency. Thus, the effects of quinpirole on ethanol and sucrose-reinforced responding were similar on response total and duration, but differential on response latency and rate. Raclopride (0.05 and 1.0 microgram/microliter) decreased total ethanol responding and rate, but doses as much as 400-fold greater (20.0 micrograms/microliter) did not alter sucrose response totals. Raclopride alone had no effect on response latency or duration measures in either reinforcement condition. Coadministration of raclopride blocked the quinpirole-induced increase in response latency (ethanol reinforcement) and decrease in response rate (sucrose reinforcement), but had no effect on other response measures. These data are consistent with the interpretation that D2 and D3 receptors in the mPFC are differentially involved in ethanol and sucrose response onset and maintenance, but similarly involved in response termination. However, differences in baseline response parameters and group size may have contributed to the observed effects.