To study the potential usefulness of technetium-99m hexakis-2-methoxy-2-methylpropyl-isonitrile (Tc-MIBI) as a cardiac perfusion imaging agent, the left circumflex coronary arteries of 12 dogs were partially occluded. Eight additional control dogs had no coronary artery stenosis. Myocardial Tc-MIBI activities in the left circumflex and left anterior descending zones were continuously monitored by miniature implantable radiation detectors for 4 hr after administration of the isotope. The dogs were then killed. Serial gamma camera images were also acquired during the study. Heart rate, arterial blood pressure, pressure distal to the stenosis, and cardiac output did not change significantly during the experiment. Microsphere-determined regional myocardial blood flow was significantly reduced in the left circumflex distribution in the 12 dogs with coronary artery stenoses. In the 12 dogs with left circumflex coronary artery stenoses, the 4 hr fractional Tc-MIBI clearances from the normal and ischemic zones were minimal and equivalent (0.15 +/- 0.05 vs 0.15 +/- 0.07). In the eight control dogs, 4 hr fractional Tc-MIBI clearances from the left anterior descending and left circumflex artery zones were minimal and equivalent (0.11 +/- 0.06 vs 0.10 +/- 0.07). Four hour fractional Tc-MIBI clearance from the blood was 0.98 +/- 0.03 for the dogs with stenosis and 0.97 +/- 0.02 for the dogs without stenosis. One additional dog had complete occlusion of the left circumflex coronary artery followed by administration of Tc-MIBI and scandium-46-labeled microspheres. This heart was immediately sectioned and counted to determine the relationship of regional blood flow to Tc-MIBI distribution (r = .92).(ABSTRACT TRUNCATED AT 250 WORDS)