An intravenous bolus injection of nicotine (1 mg/kg) markedly elevated gastric acid secretion; oral administration of ethanol (40%, 10 ml/kg) significantly increased arterial serum gastrin and somatostatin levels. Chronic pretreatment with oral nicotine (5 or 25 µg/ml in drinking tap water, for 10 days), but not acute pretreatment with a single oral dose of nicotine (2 or 4 mg/kg), inhibited the nicotine-induced gastric acid secretion and ethanol-induced gastrin and somatostatin release. Pretreatment subcutaneously with a ganglion-blocking dose of hexamethonium (10 mg/kg), however, inhibited nicotine-stimulated acid output and ethanol-evoked somatostatin secretion but not ethanol-induced gastrin release. It is concluded that ethanol-evoked gastrin secretion could be due to activation of specific sites which are not nicotinic receptors, but which are depressed by chronic nicotine pretreatment. On the other hand, the release of somatostatin by ethanol appears to be controlled by ganglionic receptors in the gut.