1. Ethanol decreases the release of acetylcholine through effects on presynaptic neurons at both muscarinic and nicotinic junctions. 2. Blockade of the release of acetylcholine should produce denervation supersensitivity at both muscarinic and nicotinic cholinergic junctions. 3. Chronic but not acute treatment with ethanol produces supersensitivity to the hypothermic effects of a muscarinic agonist in the rat. 4. The authors now report that chronic treatment with orally administered ethanol blunts (rather than enhances) the hypothermic response to nicotine in the rat. 5. This could have major public health implications. 6. Smoking and the use of ethanol containing beverages positively covary. 7. Ethanol induced reduction in sensitivity to nicotine suggests that the heavy consumption of ethanol may necessitate that one drink more than otherwise in order to obtain the desired effects of nicotine.