To assess whether a cardiac lymphagogue, CLS 2210, would reduce myocardial infarct size after coronary artery ligation, studies were performed in 14 dogs. The left anterior descending coronary artery was ligated in each dog, and the dogs were randomized to either placebo or CLS 2210 treatment, which was carried on for seven days. After seven days the animals were sacrificed and the volume of infarcted myocardium was determined macroscopically on a double-blind basis, supported by histologic examination. CLS 2210 treatment resulted in a highly significant reduction in the volume of infarcted myocardium (p less than 0.001). Since CLS 2210 is chemically and pharmacologically unrelated to hyaluronidase but shares an action with hyaluronidase as a cardiac lymphagogue, the results offer further support for a role of myocardial lymphatics in the evolution of myocardial necrosis following coronary artery occlusion and provide an explanation for the mechanism by which these agents reduce myocardial infarction size.