There is a great deal of evidence suggesting that endogenous opioid systems are involved in the control of ethanol-seeking behavior and reward. To ascertain the role of the enkephalinergic opioid peptide system in these processes, we examined voluntary ethanol consumption patterns in mice lacking the preproenkephalin (Penk) gene using a two-bottle choice paradigm with free access to water and increasing concentrations of ethanol (2, 4, 8, and 10% v/v). We also examined the ability of ethanol (2 g/kg i.p.) to establish a conditioned place preference in these mice. No differences in ethanol consumption or preference were observed between wildtypes and Penk null mutant mice. In addition, both genotypes displayed a similar conditioned place preference to ethanol. These data suggest that the preproenkephalin system is not involved in voluntary ethanol consumption patterns or ethanol reward.