We investigated whether prolonged infusion of hypertonic mannitol results in a sustained increase in coronary flow and reduces myocardial necrosis after ventriculotomy or two hours of circumflex coronary artery occlusion. Cardiac outputs, intracardiac pressures, and heart rates did not differ between mannitol and control animals. Those receiving mannitol after ventriculotomy had coronary flows to myocardium near the incision which did not differ from controls. During coronary occlusion, mannitol did increase flow to ischemic and peri-ischemic regions by one hour, but this increase was not sustained at two hours. On histologic examination, myocardial necrosis involving the right ventricular free wall in the ventriculotomy animals and the posterior papillary muscle and subadjacent free wall in the coronary occlusion animals, did not differ between the mannitol treated and control groups. The data obtained in the present study, combined with those from earlier evaluations of the influence of mannitol during ventriculotomy and myocardial ischemia, suggest that mannitol's ability to increase coronary flow to injured areas of myocardium is relatively short-lived.