Because tacrine, a cognitive enhancing agent, was being considered for approval for use in Alzheimer's disease, its possible interaction with ethanol, a commonly used substance to which elderly individuals are generally more sensitive than younger individuals, was explored. For purposes of comparison, two other drugs, which have also been shown to improve memory in mice, at doses which had activity in a working memory paradigm, were evaluated for an interaction with ethanol. Ethanol-induced sedation in mice was increased by tacrine and decreased by physostigmine, whereas AIT-082 did not alter sedation. However, tacrine had no effect on body temperature or on ethanol-induced hypothermia. Neither tacrine nor physostigmine had any effect on the rate of ethanol elimination from the blood. As tacrine comes into clinical use in the treatment of Alzheimer's disease, adverse interactions with ethanol should be explored further.