To study the efficacy of a single bedtime dose of H2-receptor antagonist in the healing of duodenal ulcer, a 12-week randomized double-blind controlled trial of oxmetidine, which is equipotent to cimetidine and has a similar duration of action, was performed in 80 patients. Oxmetidine, 600 mg bedtime, resulted in significantly more complete healing than placebo at weeks 2, 4, 6, 8, 10, and 12 as assessed endoscopically. At weeks 4 and 6, 72.5% and 85%, respectively, of ulcers were completely healed by oxmetidine, and 36.8% and 41.7%, respectively, by placebo. Of 45 prospectively obtained patient characteristics, high pentagastrin-stimulated maximal acid output and large ulcer diameter significantly affected healing adversely. These results indicate that duodenal ulcer healing may be achieved by reducing the nocturnal acid secretion alone.