We examined the ability of sucralfate to prevent secretagogue induced duodenal ulcer in the rat. Sucralfate was administered orally in dosage schedules of 50 mg, 100 mg or 200 mg before and at 3 and 6 hr after commencing a 24 hr continuous infusion of pentagastrin and bethanechol. The animals were sacrificed at 24 hr and the number and severity of ulcers was scored. Ulcers developed in all 9 control rats, in 8 of 9 on the 50 mg dose, in 4 of 9 on the 100 mg dose, and in only 1 of 9 on the 200 mg dose of sucralfate. We conclude that sucralfate prevents the formation of secretagogue induced duodenal ulcer in the rat.