Esophageal hypersensitivity is one of the most common causes of non-cardiac chest pain in patients. In this study, we investigated whether exposure of the esophagus to acid and other chemical irritants affected activity of thoracic spinal neurons responding to esophageal distension (ED) in rats. Extracellular potentials of single thoracic (T3) spinal neurons were recorded in pentobarbital anesthetized, paralyzed, and ventilated male rats. ED (0.2, 0.4 ml, 20 s) was produced by water inflation of a latex balloon placed orally into middle thoracic region of the esophagus. The chemicals were administered via a tube that was passed through the stomach and placed in the thoracic esophagus. To irritate the esophagus, 0.2 ml of HCl (0.01 N), bradykinin (10 µg/ml), or capsaicin (10 µg/ml), were injected for 1-2 min. Only neurons excited by ED were included in this study. Results showed that intraesophageal instillation of HCl, bradykinin and capsaicin increased background activity in 3/20 (15%), 7/25 (28%), and 9/20 (45%) neurons, but enhanced excitatory responses to ED in 9/17 (53%), 8/15 (53%) and 7/11 (64%) spinal neurons, respectively. Furthermore, intraesophageal chemicals were more likely to enhance the responsiveness of low-threshold than high-threshold neurons to the esophageal mechanical stimulus. Normal saline (pH 7.4, 0.2 ml) or vehicle instilled in the esophagus did not significantly affect activity or ED-responses of neurons. It is concluded that enhanced responses of thoracic spinal neurons to ED by the chemically challenged esophagus may provide a possible pathophysiological basis for visceral hypersensitivity in patients with gastroesophageal reflux and/or esophagitis.