The pedunculopontine tegmental nucleus (PPN) has been implicated in a variety of behavioral functions, including stimulus selection. Given the PPN interactions with the mesolimbic system, it was considered important to determine its involvement in ethanol self-administration. Long-Evans male rats were trained to self-administer 10% ethanol by using a sucrose-substitution procedure. After implantation of cannula guides, microinjections of 30, 100, and 300 ng of muscimol into the PPN before the self-administration session were performed. Ethanol self-administration was decreased at the 300-ng dose, in a manner similar to the actions of dopamine agonists microinjected in the nucleus accumbens. It is hypothesized that loss of PPN cholinergic input to the mesolimbic system affects the integrative activity of the nucleus accumbens and underlies the observed change in ethanol self-administration behavior.