In myocardial perfusion imaging, multiple-vessel involvement of coronary artery disease (CAD) sometimes makes diagnosis difficult. Transient left ventricular (LV) dilatation on Tl-201 myocardial SPECT is a useful finding that enables the clinician to identify patients with multiple-vessel disease. The aim of this study was to confirm the utility of measuring transient LV dilatation for the detection of multiple-vessel CAD in exercise Tc-99m tetrofosmin myocardial SPECT. The participants were 55 CAD patients and 20 controls who underwent Tc-99m tetrofosmin myocardial SPECT exercise and resting imaging. During exercise, 370 MBq (10 mCi) Tc-99m tetrofosmin was injected. Exercise images were obtained 30 minutes after injection. At 210 minutes after injection, 740 MBq (20 mCi) Tc-99m tetrofosmin was administered intravenously. The rest SPECT images were acquired 30 minutes later. Thirty-six radii at every 10 degrees were generated from the center of short-axis images. An area surrounded by 36 maximal points of the myocardial Tc-99m tetrofosmin counts on each radius was calculated for exercise and rest images. The area surrounded by the 36 maximal points in the same slice of the exercise and rest images was assigned the variables A (Ex) and A(R), respectively. The transient dilatation index (TDI) of the left ventricle was calculated using the formula mean A (Ex)/A(R) in the apical, middle, and basal myocardial short-axis images. In the controls, the TDI was 0.970 +/- 0.021. In patients with CAD, the TDIs of one-vessel disease, two-vessel disease, and three-vessel disease were 1.034 +/- 0.032, 1.093 +/- 0.046, and 1.131 +/- 0.076, respectively. The TDIs were significantly greater in patients who had more occluded coronary arteries (P < 0.01). If the mean + 2SD of the TDI (1.012) in controls were assumed to be the normal upper limit, the sensitivity, specificity, and accuracy of this method in detecting two-vessel or three-vessel disease would be 91.4%, 76.9%, and 84%, respectively. The TDI is a useful index for evaluating subendocardial ischemia non-invasively and detecting multiple-vessel disease clinically.