The ability of hyperosmolar mannitol to salvage evolving myocardial infarction was studied in 50 open-chest dogs subjected to 3 hours occlusion of the left anterior descending coronary artery. In 28 dogs, 20% hyperosmolar mannitol was infused into the distal half of the infarcted portion after commencement of reperfusion, leaving the proximal half mannitol free. In the other 22 dogs, physiological saline was infused instead of mannitol. The wall thickness at the distal half of the infarcted portion was increased 2 hours after reperfusion in both the saline and the mannitol groups. After 2 hours reperfusion the chest was closed. Thirteen out of 28 dogs in the mannitol group and 12 out of 22 dogs in the saline group died over one week. Seven days later, myocardial samples were measured for myocardial water content and creatine phosphokinase activity (CPK). Myocardial water content was increased in the infarcted portion in both the saline and the mannitol groups. In the saline group, myocardial CPK was reduced markedly in the proximal half (54.8 +/- 7.8% at the inner layer and 53.1 +/- 4.7% at the outer layer). These depletions were even more marked in the distal half (47.9 +/- 5.8 and 48.3 +/- 3.3%). In the mannitol groups, although the CPK was similarly depressed in the proximal half (44.8 +/- 5.8 and 41.1 +/- 5.4%), the CPK depletion in the distal half was less (48.1 +/- 6.1 and 58.1 +/- 6.7%) than the proximal half, suggesting mannitol preserved CPK depletion in the infarcted portion. It was concluded that intracoronary infusion of mannitol after reperfusion may salvage the infarcted myocardium.