Technetium-99m-sestamibi, a new myocardial perfusion imaging agent, does not show significant or rapid myocardial redistribution following its intravenous injection at stress. The purpose of this study was to evaluate the myocardial clearance of 99mTc-sestamibi and ischemic/normal wall ratios at 1 hr and at 3 hr after injection at stress in patients with significant coronary artery disease. Twenty-five patients with ischemic defects on 201Tl scans (n = 15) and/or significant disease on coronary angiogram (n = 18) were prospectively studied. Planar images were obtained at 65 and at 190 min after an injection at stress of 20-25 mCi of 99mTc-sestamibi. A rest study was performed 1-6 days later. Ischemic/normal wall ratios were 0.73 +/- 0.10 and 0.83 +/- 0.12 (p less than 0.05) at 1 and 3 hr, respectively (0.98 +/- 0.15 at rest). Myocardial washout was 26% +/- 12% for normal walls and 15% +/- 8% for ischemic walls (p less than 0.001). Segmental analysis showed 48 and 46 ischemic segments at 1 and 3 hr, respectively. In conclusion, although only a few ischemic segments were missed at 3 hr, significantly lower ischemic/normal wall ratios were found at 1 hr. Faster myocardial washout from normal walls is responsible for the partial reduction of this ratio.