The safety and efficacy of sucralfate (an aluminum salt of sucrose sulfate) in duodenal ulcer treatment were assessed in a double-blind, placebo-controlled, multicenter study. Out-patients received two 500 mg sucralfate tablets or placebo tablets after meals and at bedtime. Endoscopic examinations were performed in 216 patients, either after 2 weeks or 4 weeks, or both, to evaluate healing. After 2 weeks, 35% (37 of 105) of th sucralfate patients had complete healing, compared to 25% (26 of 106) of the placebo patients (p = 0.0225, Mantel-Haenszel). After 4 weeks, the sucralfate and placebo rates were 75% (82 of 109) and 64% (68 of 107), respectively (p = 0.0383). Patients in the sucralfate group reported greater reduction in both diurnal and nocturnal pain each week than those in the placebo group. No serious side effects were reported with sucralfate use; the most common complaint was constipation in 2.6% of the sucralfate patients assessed. Laboratory tests--conducted pretreatment, after 2 weeks, and after 4 weeks--revealed no evidence of adverse effects. The nonsystemic agent appears to represent a unique, safe, and effective mode of treatment for duodenal ulcer.