Ethanol, self-administered orally, has been shown to serve as an effective reinforcer in several species. Self-administration studies have also illustrated that ethanol-drinking behavior can be conceptualized as a specific type of operant behavior. The use of inbred and selectively bred animals in other areas of alcohol research has provided valuable information about the contribution of genetic factors to ethanol-related behaviors. Our research was designed to study genetic differences in oral self-administration in the ALKO AA (Alcohol Accepting) and ANA (Alcohol Non-Accepting) rat lines, selected for ethanol preference. Thus, we applied a behavior genetic analysis to aid in determining the contribution of genetic factors to behavior, specifically drug-seeking behavior. The results of our experiments indicate that genetic differences are important factors contributing to the establishment of a drug as a reinforcer. At least in the case of ethanol, the drug did not act as a reinforcer in non-preferring animals. Conversely, in preferring animals, ethanol was readily established as a reinforcer.