The mechanisms by which transforming growth factor- (TGF-) protects the stomach against mucosal injury are incompletely understood. The aim of this study was to examine the roles of sensory neurons, sensory neuropeptides and prostaglandins in TGF gastroprotection against ethanol. Fasted rats received TGF- (50 g/kg, intraperitoneally) prior to orogastric ethanol (75% v/v, 1 ml). Gastric injury was quantitated 30 min after ethanol. Involvement of sensory neurons and the sensory neuropeptides, calcitonin gene-related peptide (CGRP) and substance P (SP), were examined by capsaicin deafferentation and specific receptor antagonist infusion, respectively. Indomethacin (10 mg, intragastrically) was used to determine the role of prostaglandins in TGF--mediated gastroprotection. TGF- significantly diminished ethanol-induced gastric lesion area to 5.7 ± 0.8 mm² vs 4l.1 ± 5.2 mm² (P < 0.001).="" sensory="" denervation="" and="" cgrp-receptor="" blockade="" abolished="" the=""> protective effect. In contrast, SP antagonist and indomethacin did not alter TGF- gastroprotection. In conclusion, TGF--mediated gastroprotection involves sensory neuron activation and CGRP release and this protective effect did not involve substance P or prostaglandin generation.