In a prospective multicenter trial, 43 patients with acute duodenal ulcers unhealed after four weeks of treatment with an H2-receptor antagonist, ranitidine, were switched to treatment with another H2-receptor antagonist, cimetidine. Sixty-eight percent of the unhealed patients were successfully healed; of these patients, 81% were free of daytime pain and 89% were free of nighttime pain. Of those with residual pain, 71% and 50% showed improvement in daytime and nighttime pain severity, respectively. There were no unexpected adverse reactions reported or clinically significant changes in laboratory values measured during the study. It is concluded that cimetidine is highly effective both in healing duodenal ulcers unresponsive to ranitidine therapy and in providing continued relief of daytime and nighttime pain.