The hexakis(isonitrile)technetium(I) analog [99mTc]carbomethoxyisopropyl isonitrile (CPI) has high myocardial uptake and rapid lung and liver clearance in most animal species. To evaluate [99mTc]CPI as a myocardial imaging agent in the human, we evaluated this tracer in three normals and in six patients with coronary artery disease (CAD). In normals, [99mTc]CPI cleared quickly from the lungs and accumulated in the liver and heart. The liver activity peaked at 10-15 min and cleared through the hepatobiliary system. Planar images were of excellent technical quality with high myocardial to background ratios as early as 10 min after injection. Myocardial activity fell gradually to 76.1 +/- 2.9 (s.d.)% of initial activity by 60 min after injection. In six patients with CAD, myocardial defects were present on planar images up to 2 hr after exercise and injection. In one out of six patients, the defect was not seen 3 hr after injection. In five of the six patients, normal perfusion patterns were observed 1 hr after reinjection of CPI at rest (4 hr after the initial injection). In one patient who developed spontaneous angina prior to reinjection, the perfusion defects persisted. The repeat study 3 days later with injection of [99mTc]CPI at rest was normal. Technetium-99m CPI appears to have excellent physical and biologic properties for use in association with myocardial imaging with exercise.