The value of mucosal protection with sucralfate in cases of gastric ulceration is well documented. Although sucralfate is advocated as treatment of esophageal lesions, we found it to be of limited value in the management of radiation-induced esophagitis; in a pilot study of 10 cases, minor relief of symptoms, with analgetics still required, was noted in 4 patients, and no improvement was seen at endoscopy after 6 weeks of treatment in any patient. To see if this might be the result of inadequate mucosal coating, we administered sucralfate labeled with technetium 99m to 26 patients with endoscopically proven esophagitis secondary to irradiation for esophageal carcinoma. The degree of coating was evaluated according to persistence of the radionuclide in the affected esophageal segment. Scans were performed at regular intervals for 120 minutes after administration of 150 MBq 99mTc-sucralfate. Although scans were positive for radioactivity in 24 of 26 (92%) patients, only 8 (31%) of these represented selective binding of sucralfate to tissue. In the other 16 cases, scans were positive for sucralfate and albumin, indicating nonspecific retention most likely caused by concomitant esophageal stenosis. Residual radioactivity was observed for 30 minutes or more in 11 (42%) patients, but scans were positive for radioactivity after 1 to 2 hours in only 4 (15%). The duration and intensity of tracer accumulation were similar in both acute lesions an chronic radiation damage. These findings suggest that the inability of sucralfate to alleviate irradiation-induced odynophagia may be related to insufficient duration of adherence of this compound to damaged esophageal mucosa.