Aspirin (acetylsalicylic acid) has inhibitory effects on platelet function and prostaglandin synthesis. Since alterations in either platelet function or prostaglandin-mediated vascular responses could influence blood flow to ischemic myocardium, the authors tested the effects of aspirin on coronary collateral flow after acute occlusion of the left anterior descending coronary artery in dogs. Aspirin dose (600 mg i.v.) consistently inhibited in vitro ADP-induced platelet aggregation. In 13 open-chest dogs, regional myocardial blood flows (radioactive microsphere technique) were determined at 5 minutes and 4 hours after occlusion. In seven of these dogs, aspirin (600 mg i.v.) was administered 1 hour before occlusion. In the aspirin-treated dogs, collateral flow increased significantly (p<0.05), from 0.09±0.02 ml/min/g at 5 minutes to 0.15 and 0.02 ml/min/g 4 hours after occlusion. Collateral flow was not significantly altered over 4 hours in control dogs. The aspirin induced increase in collateral flow was confined to epicardium (12±4% of normal zone flow at 5 minutes to 23 ±4% at 4 hours after occlusion).