Endoscopically controlled measurement of gastric mucosal potential differences was performed in 50 subjects receiving ranitidine, cimetidine or normal saline. Significant maximum potential increases were recorded within 15 min of bolus injections of ranitidine in doses of 20 and 40 mg and cimetidine (200 and 400 mg). Under these conditions, ranitidine proved to be 12 times more potent than cimetidine, compared on a molar basis. There was a dose-related increase in serum prolactin concentration within 15 min of injection of 200 and 400 mg of cimetidine, while injections of 20 and 40 mg of ranitidine failed to enhance prolactin secretion. It would appear that the stimulatory effect of cimetidine on serum prolactin concentration is not mediated through its histamine H2-receptor antagonist activity.