The introduction of over-the-counter histamine2 -receptor antagonists (H2 -RAs) makes it important to characterize these agents in terms of their different times to onset of action and magnitude of effect. The time to onset of action and the degree of gastric acid inhibition of the H2 -RAs famotidine and cimetidine at dosage levels approved for over-the-counter use (10 mg famotidine and 200 mg cimetidine) were compared. Twenty-four subjects with a history of heartburn of at least 2 months duration received 10 mg famotidine, 200 mg cimetidine, or placebo in a randomly assigned sequence of three treatment periods. Each period began with an overnight fast, followed by insertion of an intragastric pH probe during a 1-hour baseline monitoring phase, and, 1 hour later, administration of the test medications and monitoring of intragastric pH for an additional 2-hour period. The onset of acid inhibition occurred approximately 35 minutes after administration of either famotidine or cimetidine. Famotidine provided a significantly greater degree of efficacy on all three parameters monitored: percentage of time that gastric pH values were greater than 3.0, mean area-under-the-pH-curve-versus-time curve, and median pH (obtained at 5-minute intervals). Clearly, the over-the-counter dosage of famotidine (10 mg) provided gastric pH elevations that were as rapid and of superior degree than those induced by cimetidine 200 mg.