Myocardial perfusion imaging with Tc-99m carbomethoxyisopropylisonitrile (CPI) was compared with Tl-201 imaging in 22 patients who were assessed for coronary artery disease. There was agreement between Tc-99m CPI and Tl-201 imaging for detecting segmental myocardial ischemia and fixed defects in 185/198 (93%) of left ventricular segments. There was also an excellent correlation between the two tracers for the detection of coronary artery disease (18/22 patients). Myocardial clearance of the isonitrile complex was slow, and there was no redistribution into ischemic regions; the normal to ischemic myocardial ratio remained relatively constant over time. Reinjection at rest was used to distinguish transient ischemia from infarction. The isonitrile complex was excreted rapidly via the hepatobiliary system. After 3 hours, background activity was reduced to about 20% of the initial activity. Tc-99m CPI appears comparable to Tl-201 thallous chloride for detecting coronary artery disease. Tc-99m CPI may be useful as a myocardial imaging agent because there is no myocardial redistribution, myocardial clearance is slow, and clearance from background tissues is rapid.