Clinical studies suggest that sulfinpyrazone and aspirin may be useful in the treatment of coronary artery disease. It was previously shown that pretreatment with a completely platelet-inhibitory dose of aspirin is associated with increased epicardlal collateral flow 4 hours after coronary occlusion in dogs. In this study evaluation was made of platelet inhibitory doses of sulfinpyrazone (30 mg/kg) and aspirin (3 mg/kg) and an aspirin dose (30 mg/kg) 10-fold greater than the minimal dose necessary for complete platelet inhibition. Collateral flow (ml/min per g) was measured 5 minutes after temporary (pretreatment) occlusion of the left anterior descending coronary artery. After release of the occlusion and recovery, a drug dose or saline solution was given, permanent (post-treatment) occlusion instituted, and flow measurement repeated 5 minutes and 4 hours later. Administration of sulfinpyrazone (11 dogs) caused an increase in flow to the ischemic epicardium from 5 minutes after the pretreatment occlusion to 5 minutes after the post-treatment occlusion (mean ± standard error of the mean): Δ = 0.09 ± 0.02, p < 0.01. However, a significant increase was not found in the control group (11 dogs) or in either aspirin-treated group (8 dogs each). All the drug doses caused a significant increase in epicardial collateral flow from 5 minutes after the post-treatment occlusion to 4 hours after the same occlusion: sulfinpyrazone, Δ = 0.08 ± 0.03, p < 0.025; aspirin, 3 mg/kg, Δ = 0.16 ± 0.06, p < 0.05; and aspirin, 30 mg/kg, Δ = 0.14 ± 0.05, p < 0.05. No significant increase was observed during the same interval in control dogs. Endocardial collateral flow 4 hours after post-treatment occlusion was slightly increased in relation to pretreatment values in the sulfinpyrazone group but not in any of the remaining groups. Enhanced collateral flow after coronary occlusion may contribute to some of the beneficial effects ascribed to sulfinpyrazone and aspirin in coronary artery disease.