We have previously shown that short-term (15–20 min) low dose (1–2%) ethanol exposure inhibits secretagogue-induced acid secretion. In the present study we investigate the potential interactions of ethanol with AMP-Kinase (AMP-K), a potent modulator of energy-dependent processes in a variety of cells. Individual rat gastric glands were incubated with the pH-sensitive dye BCECF. The secretagogues carbachol or histamine (200μM) were added during dye-loading and to all solutions. Following loading, glands were subsequently exposed to an NH4Cl prepulse (20mM) and a 0mM Na+ solution. Rates of alkalinization were calculated as dpHi/dT. In one series of experiments ethanol was added to all solutions and the rate of alkalinization compared to secretagogues alone. In a separate series ethanol was added in combination with compound C (20μM) an AMP-K inhibitor to prevent activation of the AMP-K. Ethanol significantly suppressed secretagogue-induced acid secretion. Addition of compound C reversed the inhibitory effects of ethanol on secretagogue-induced acid secretion. We demonstrate that low dose ethanol inhibits secretagogue-dependent acid secretion by activation of the AMP-K pathway in rat gastric parietal cells. This inhibition can be reversed by exposure to the AMP-K inhibitor compound C, further suggesting a strong link between ethanol and AMP-K activation. This work was supported by the Ohse Fund.