Alcohol is consumed orally by humans, and oral self-administration has been successfully modeled in laboratory animals. Over the last several years, attempts have been made to develop a procedure for the reliable intravenous (IV) self-administration of alcohol in rodents. IV self-administration would provide a better tool for investigating neurobiological mechanisms of alcohol reinforcement and dependence because confounding factors associated with oral self-administration, such as variations in orosensory sensitivity to alcohol and/or its absorption, are avoided. A review of the literature shows that rats, mice and non-human primates can initiate and maintain IV self-administration of alcohol. However, there are 50- to 100-fold interspecies differences in the reported alcohol infusion doses required. Most surprising is that the infusion dose (1-2 mg/kg) that reliably maintains IV alcohol self-administration in rats results in total alcohol intakes of only 20-25 mg/kg/hour, which are unlikely to have significant pharmacological effects. The evidence to support IV self-administration of such low doses of alcohol in rats as well as the potential biological mechanisms underlying such self-administration are discussed. The minute amounts of alcohol shown to reliably maintain IV self-administration behavior in rats challenge the relationship between their blood alcohol levels and the rewarding and reinforcing effects of alcohol.