To study the comparative value of the levels of cardiac troponin I (cTnI), creatine kinase-MB isoenzyme (CK-MB), and myoglobin in the detection of acute ischemic myocardial injury, we serially measured plasma concentrations of these cardiac proteins in 12 pigs with myocardial ischemia subtending severe coronary artery stenoses and in 5 pigs with a sham operation performed, but without coronary artery stenosis. In the stenosis group, flow in the left anterior descending (LAD) artery was reduced by 36% and maintained for 24 hours (n = 3), 7 days (n = 6), or 4 weeks (n = 3). Flow in the coronary artery was measured by a flowmeter, and regional left ventricular dysfunction was monitored by echocardiography. Myocardial infarction was identified with triphenyltetrazolium chloride staining. All pigs with stenosis of the LAD had significant ultrastructural abnormalities consisting of loss of myofibrils and an increase in mitochondria and glycogen deposition. Cardiac proteins were released in all pigs with stenosis of the LAD artery during the development of myocardial ischemia; the levels of cTnI, CK-MB, and myoglobin increased significantly relative to the baseline. The sensitivity and specificity for cTnI were higher than for CK-MB or myoglobin. Results of this study show that cTnI is the better marker for the detection of acute ischemic myocardial injury. Increased levels of cTnI can be found in reversible and irreversible myocardial ischemic injury in this model.