This study was undertaken to assess the clinical usefulness of a single nighttime dose of ranitidine in the short-term healing of duodenal ulcer. One hundred and nine patients with endoscopically diagnosed duodenal ulcer were randomly allocated to treatment with ranitidine, either 150 mg twice daily or 300 mg as a single nighttime dose for four weeks, in a prospective double-blind, double-placebo trial. Of the 102 patients who completed the study, 48 of 57 (84 percent) healed endoscopically on ranitidine 150 mg twice daily, and 43 of 45 (96 percent) healed on 300 mg at nighttime (Mantel-Haenszel test without continuity correction: X2 = 2.9, p = 0.09). One patient treated with ranitidine 150 mg twice daily had a transient episode of cholestatic hepatitis that did not necessitate stopping the drug; in this patient the ulcer healed after 28 days of treatment. There were no other unwanted effects in either group and no significant abnormal biochemical or hematologic changes. This study shows that ranitidine 300 mg given as one nighttime dose is as safe as 150 mg twice daily, and equally as effective. Three hundred milligrams at night appear to confer protection against the adverse effect of smoking in ulcer healing.