One hundred twenty-eight beagle dogs were randomized to receive thoracic irradiation with doses between 0 and 72 Gy in 1.5-Gy fractions over 6 weeks. Dogs were randomized to have either 33, 67 or 100% of their lung volume irradiated. The entire thoracic portion of the esophagus and variable portions of the fundus of the stomach were included in the treatment field at all volumes. Sixteen of the 128 dogs entered in the study developed clinical signs of esophagitis. These 16 dogs received doses between 45 and 72 Gy. Clinical signs of esophagitis/gastritis included dysphagia, anorexia, emesis, excessive salivation and weight loss that required force-feeding of a liquid diet. An ED50 of 67.2 Gy (95% CI 61.45-79.7 Gy) was calculated for the occurrence of clinical signs that required some supportive treatment. Three of the 16 dogs receiving 63 or 72 Gy failed to respond to treatment and were euthanized. Twenty-five other dogs were euthanized prior to 2 years due to other treatment-related complications. Two dogs died of causes not related to treatment. No late esophageal complications were observed in the remaining 98 dogs out to 2 years after irradiation. Esophageal specimens from 79 dogs were available for quantitative histological analysis 2 years after irradiation. Histological analysis showed a decrease in the percentage of glandular tissue with a corresponding increase in lamina propria and muscle.