This case report documents severe esophagitis and rapid esophageal stricture formation in a man infected with the human immunodeficiency virus (HIV) who was treated with standard thoracic irradiation for locally advanced non-small-cell lung cancer. Severe late esophageal toxicity is a rare complication of radiation therapy in patients who are HIV negative, but those who are HIV positive may be at increased risk. This article reviews the literature suggesting that HIV infection may lead to unusually severe radiation-induced mucosal injury. High-dose chest irradiation should be performed with caution in this group of patients.