Upper gastrointestinal tract mucosal irritations, such as esophagitis, have been reported as rare adverse events due to a variety of aminobisphosphonates, including alendronate sodium, which have been widely used to treat osteoporosis. Although the pathogenesis of aminobisphosphonate-induced esophageal mucosal irritation has not been clearly understood, direct chemical esophageal irritation with prolonged local mucosal exposure to the drug with gastric contents might be the most plausible mechanism according to the previously reported literature. Here we report a young adult man with severe ulcerative esophagitis due to alendronate who demonstrated a strongly positive result on a drug lymphocyte stimulation test against alendronate. This case report provides the new concept that T-cell mediated delayed hypersensitivity to the drug may be involved in the pathogenesis of alendronate-induced esophagitis.