Myocardial clearance of the new cationic, lypophilic myocardial perfusion agent, Tc-99m-hexakis-2-methoxy-2-methylpropyl isonitrile (MIBI) was studied in nine patients with coronary artery disease. Regional time-activity curves were determined from serial postexercise myocardial SPECT images after a single dose of Tc-99m MIBI. There were significant differences between the clearance rates from normal and ischemic myocardium. Tc-99m MIBI washout from normal myocardium was 27 +/- 8% by 6 hours after injection. Clearance from mild myocardial defects (initial activity greater than 60% of the activity in normal myocardium) was 16% by 6 hours in six patients. No washout was detected by 6 hours in the three patients with severe myocardial defects. The ratio between the activity in ischemic and normal myocardium increased from 0.70 +/- 0.08 to 0.80 +/- 0.13 and 0.84 +/- 0.13 at 4 and 6 hours after injection in the patients with mild defects. In the patients with large defects, the ratio increased from 0.42 +/- 0.09 to 0.54 +/- 0.07 at 6 hours. It is concluded that, while redistribution is substantially slower than with Tl-201, image interpretation and data evaluation should be approached cautiously when imaging is delayed 4 hours or more after injection of Tc-99m MIBI. Quantitative techniques aimed at evaluating the extent and intensity of myocardial ischemia will be particularly affected.