In man, oral administration of coffee (277 mg caffeine) caused a striking increase in gastrin secretion, as measured by radioimmunoassay. The radioimmunologically measurable insulin and blood glucose remained unaffected. In response to oral ingestion of ethanol, only a slight but biologically not impressive gastrin and insulin increase was found. Intragastric cooling did not have any distinct bearing on the release of gastrin and insulin. Results indicate that gastrin is an important mediator of the stimulatory effect of caffeine on gastric acid secretion, whereas ethanol acts directly on the parietal cells by local irrigation and not via gastrin release.