Technetium-99m (To-99m) tetrofosmin, a new myocardial perfusion imaging agent, was evaluated at exercise and rest in 50 patients with documented coronary artery disease to determine myocardial kinetics, redistribution and ideal imaging time. Planar imaging was performed at 5, 30, 60, 90, 120 and 240 minutes after an injection of Tc-99m tetrofosmin (8 to 10 mCi) at peak graded ergometric exercise. Reinjection (24 to 30 mCi) was performed at rest, 4 hours after the stress injection and also on a separate day, and imaging was repeated. All patients underwent thallium-201 (TI-201) exercise and redistribution (4-hour) imaging. Perfusion defect to normal, and heart to lung ratios were calculated for exercise To-99m tetrofosmin images at each time point. The mean ± SD defect to normal ratios were 0.75 ± 0.10, 0.75 ± 0.10, 0.74 ± 0.09, 0.73 ± 0.10, 0.73 ± 0.10 and 0.72 ± 0.10 at 5, 30, 60, 90, 120 and 240 minutes, respectively (p = NS), suggesting absence of redistribution. There was a significant increase in lung uptake of TI-201 during exercise (p <0.05), but not with To-99m tetrofosmin (p = NS). Washout of To-99m tetrofosmin was calculated in a subset of patients (n = 23). Rapid background clearance enabled postexercise diagnostic imaging as early as 5 minutes after injection. Myocardial retention curves after rest injection suggested that the optimal time for imaging was approximately 30 minutes later. Slow myocardial washout (4%/hour after exercise and 0.6%/hour after rest injection) enabled diagnostic images to be obtained up to 4 hours after each study. Image quality was generally superior to that with TI-201. Tc-99m tetrofosmin has the advantage of early imaging after exercise, with no evidence of redistribution.