Hyaluronidase has been reported to be beneficial in reducing injury to the ischemic myocardium in several experimental studies. This effect may involve an enhancement in either the cardiac blood supply or lymphatic flow or a combination there of. In this experiment, a baboon open chest model of myocardial ischemia and reperfusion was used to determine if treatment with hyaluronidase would result in a reduction in infarct size. Baboons underwent occlusion of the left anterior descending coronary artery for 2 hr. Fifteen minutes after occlusion, a treated group (n = 6) received bovine testicular hyaluronidase (500 national formulary units/kg) i.v. over a 10-min period. The ischemic period was followed by 22 hr of reperfusion. A control group (n = 8) underwent the same protocol minus the hyaluronidase infusion. At the end of the reperfusion period, the hearts were excised and the perfusion bed at risk for infarction was determined by the infusion of a microvascular dye. The hearts were then sectioned and stained for the histological determination of infarct size. The volume of the perfusion bed infarcted was 66 +/- 7% in the control group compared with 42 +/- 10% in the treated group (P > 0.05). In this study using a primate model that has a minimal collateral blood supply, hyaluronidase did not significantly reduce the ultimate infarct size.