The aim of this study was to examine the effects of varying doses of pirenzepine, a selective muscarinic subtype M1 antagonist, on the prevention of acute gastric mucosal lesions in male Sprague-Dawley rats subjected to spinal cord section at the C7 level. It was also intended to evaluate the effects of the drug on gastric acid output and gastric mucosal blood flow. Pirenzepine 1, 2.5 and 5 mg/kg every 2 h all caused a significant reduction in mean total ulcer length (p less than 0.01) compared to controls. This was associated with a significant decrease in acid output (p less than 0.05). There was no significant effect on gastric mucosa blood flow as measured by hydrogen gas clearance. These results indicate that the protective effects of pirenzepine on gastric mucosa, in the spinal rat model, are associated with the acid-inhibitory action of the drug and not on mucosal blood flow effects.