To assess the gastric mucosal protective action of sucralfate against alcohol, a double-blind, controlled, randomized study was carried out in 12 healthy adult men. All subjects received four treatments in a random sequence: sucralfate + ethanol, sucralfate + ethanol placebo, sucralfate placebo + ethanol, and sucralfate placebo + ethanol placebo. Fundal, antral, and duodenal mucosae were submitted to endoscopic examinations, and the antral mucosa underwent histologic examination before and after injury. Biopsy specimens were taken from the antral mucosa to determine by radioimmunoassay its capacity to synthesize prostaglandin E2, thromboxane B2, and 6-keto prostaglandin F1 alpha. In both the fundus and the antrum, the mean endoscopic injury score after sucralfate plus ethanol administration was significantly lower than that after ethanol alone. All treatments tended to increase prostanoid values but 6-keto prostaglandin F1 alpha increased significantly when sucralfate was given. Sucralfate did not affect serum ethanol levels, nor did ethanol affect prostanoid synthesis. It is concluded that sucralfate provides significant protection to the human gastric mucosa against ethanol injury, and that this may be partly due to increased prostanoid synthesis.