We have investigated the hypothesis that neuropeptide Y (NPY) is released from noradrenergic sympathetic nerves during experimentally induced myocardial infarction. A left thoracotomy was performed, the left main coronary artery ligated, and the animals sacrificed 4 or 48 h later. NPY levels in heart tissue from these rats and sham-operated controls were measured with radioimmunoassay. Levels of NPY in the right atrium were greater than other regions of the rat heart. After ligation of the left coronary artery, the concentration of NPY in the infarcted area of the left ventricle was reduced at 4 and 48 h when compared to a similar area in sham-operated rats. NPY levels in the septum were unchanged. The results suggest that during myocardial infarction, NPY is released from nerves in the infarcted region and may deleteriously affect increased collateral blood flow surrounding the infarcted tissue.