Acute ethanol, in both man and cats, decreases contractility of both lower esophageal sphincter (LES) and smooth muscle portion of the lower esophageal (LE) body. Because these inhibitory effects were not abolished, in cats, by cervical vagotomy or intravenous tetrodotoxin, we surmised a direct inhibitory effect of ethanol on muscle cells. Accordingly, to test this possibility, we exposed isolated, esophageal smooth muscle cells (LES and LE) to ethanol (0-150 mM) for 0 to 40 min, and then a contractile agent, carbachol, or its vehicle was added. Thirty seconds later, cells were fixed and cell shortening was measured as an index of contractility. In the absence of ethanol, carbachol dose-dependently induced shortening of muscle cells from both LE and LES. Ethanol significantly attenuated carbachol-induced maximal shortening of cells from both LE and LES. Potency for carbachol in LES (but not LE) was also decreased by ethanol. Isolated muscle cells remained viable after incubation with ethanol. Thus inhibition by ethanol: can occur directly on esophageal muscle; occurs at pharmacologically relevant ethanol concentrations; and is not simply caused by cytotoxicity of ethanol.