This prospective, randomized, double-blind study examined whether scavengers of oxygen-derived free radicals are of benefit in the treatment of acute duodenal ulceration in human beings. To this end, allopurinol (50 mg four times a day), a hydroxyl radical scavenger and an inhibitor of xanthine oxidase that forms superoxide radicals, and dimethyl sulfoxide (500 mg four times daily), a hydroxyl radical scavenger, were administered orally with cimetidine. Patients with symptomatic endoscopy-proven acute duodenal ulceration who were smokers and social drinkers were randomized to receive for 8 weeks cimetidine (400 mg two times a day), cimetidine (400 mg two times a day) with dimethyl sulfoxide, or cimetidine (400 mg two times a day) with allopurinol. These patients were then kept on their respective oral regimens (except for those who received cimetidine, for whom the dose was changed to 400 mg at bedtime) for 1 year (maintenance) and followed up for another. After 8 weeks of treatment, the ulceration healed in 69 of the patients (79%) who were given cimetidine alone and in all of the patients who were given dimethyl sulfoxide (n = 85) or allopurinol (n = 84) with cimetidine (p less than 0.01). During the maintenance year, 15 patients (29%), who were given cimetidine nightly, relapsed. Addition of dimethyl sulfoxide or allopurinol to cimetidine was associated with a significantly lower (p less than 0.001) relapse rate.(ABSTRACT TRUNCATED AT 250 WORDS)