Tolerance of esophagus to intraoperative radiotherapy (IORT) was investigated in dogs. Thirteen adult foxhounds were subjected to right thoractomy, mobilization of the intrathoracic esophagus, and IORT to a 6 cm full-thickness esophageal segment using 9 MeV electrons at doses of 0, 2,000, or 3,000 cGy. Dogs were followed clinically and were evaluated at regular intervals after treatment with fiberoptic esophagoscopy, barium swallows, and postmortem histologic evaluations. One sham-irradiated control dog showed no abnormalities during follow-up of 24 months. Seven dogs receiving 2,000 cGy IORT showed transient mild dysphagia and mild esophagitis, but no clinically or pathologically significant complications. Five dogs receiving 3,000 cGy demonstrated severe ulcerative esophagitis within 6 weeks of treatment which progressed to chronic ulcerative esophagitis with stricture formation by 9 months following IORT. One 3,000 cGy dog died at 13 months from an esophageal perforation. On the basis of a pilot experience using 13 experimental animals, it was concluded that intact canine esophagus tolerates IORT well to doses of 2,000 cGy, but doses of 3,000 cGy pose serious and potentially lethal risks. The clinical application of IORT to the treatment of human intrathoracic neoplasms requiring esophageal irradiation should be approached with caution, particularly at doses exceeding 2,000 cGy.