The effect of aspirin (20 mM.), sodium taurocholate (40 mM.), and ethanol (24 per cent w/v) on gastric mucosal blood flow was studied in an exteriorized, chambered preparation of canine fundic stomach. Gastric mucosal blood flow was measured by gamma-labeled microspheres and plasma aminopyrine clearance. All three test solutions caused a significant increase in microsphere-measured mucosal blood flow. The degree of increase in gastric mucosal blood flow was proportional to the severity of gross mucosal injury, being greatest with bile salt and least with ethanol. Plasma aminopyrine clearance determined only a small fraction of mucosal flow measured by microspheres following injury, particularly in sodium taurocholate and ethanol experiments, where the net hydrogen ion back diffusion was greatest. The results suggest that increased gastric mucosal blood flow may be a secondary defensive response to the damage caused by these irritants and that the plasma aminopyrine clearance is unreliable in quantitating mucosal blood flow changes in the presence of mucosal injury.