Infiltration of polymorphonuclear leukocytes (PMN) is associated with the progression of myocardial infarction and reperfusion injury. However, little is known about the time course of cellular infiltration. To investigate this issue, rats were subjected to 30 min of coronary artery occlusion followed by reperfusion for less than or equal to 96 h. Myocardial injury was determined by measuring the depletion of myocardial creatine phosphokinase activity, and PMN infiltration was assessed by measuring myeloperoxidase (MPO) activity. MPO activity increased from 0.7 U/g tissue in non-operated animals, to a peak of 6.7 +/- 0.8 and 6.4 +/- 1.4 U/g at 6 and 24 h after coronary artery reperfusion, respectively. MPO activity decreased to 3.3 +/- 0.8 U/g at 48 h and 1.1 +/- 0.4 U/g at 96 h, suggesting diminished PMN accumulation. Histological examination confirmed the accumulation and resolution of PMN over the 96-h period. At 24 h, there was a significant linear correlation between infarct size and MPO activity, whereas at 96 h no relationship was found. These data indicate that PMN infiltration occurs early in response to reperfusion injury and persists for only 24 h after initiation of reperfusion. These findings suggest that attempts to moderate inflammatory cell responses to myocardial injury should be administered early after coronary artery reperfusion to limit the accumulation of potentially deleterious inflammatory cells.