BACKGROUND A previous study indicated that selectively bred alcohol-preferring (P) rats self-administered ethanol (EtOH) directly into the ventral tegmental area (VTA), whereas the alcohol-nonpreferring line did not. Wistar rats will also self-administer EtOH directly into the posterior VTA. Because Wistar rats also have a low preference for EtOH solutions but self-inject EtOH into the VTA, this study was undertaken to test the hypothesis that there is an association between EtOH preference and sensitivity of the VTA to the reinforcing effects of EtOH. METHODS Adult P and Wistar rats were assigned to groups that received one of the following concentrations of EtOH: 0, 50, 75, 100, 150, or 200 mg/100 ml. Rats were connected to the microinjection system, placed into two-lever (active and inactive) experimental chambers, and given EtOH for the first four sessions (acquisition), artificial cerebrospinal fluid for sessions 5 and 6 (extinction), and EtOH again in session 7 (reinstatement). Responding on the active lever produced a 100-nl injection of the infusate. RESULTS P rats self-infused 75 to 200 mg/100 ml EtOH and demonstrated lever discrimination, whereas Wistar rats reliably self-infused only 150 and 200 mg/100 ml EtOH. Both P and Wistar rats reduced responding on the active lever when artificial cerebrospinal fluid (aCSF) was substituted for EtOH and reinstated responding in session 7 when EtOH was restored, although P rats demonstrated a very robust enhancement of responding for 100 and 150 mg/100 ml EtOH, and this was not found for Wistar rats. CONCLUSIONS These results suggest that, compared with Wistar rats, the posterior VTA of P rats was more sensitive to the reinforcing effects of EtOH. Furthermore, the reinstatement data suggest that the posterior VTA of P rats underwent neuronal alterations as a result of prior EtOH exposure and extinction that changed the reinforcing effects of EtOH within this region.