Iodine-123-iodophenyl-9-methyl-pentadecanoic acid [( 123I]MPDA) and thallium-201 (201Tl) were sequentially injected in 11 patients during exercise-induced myocardial ischemia. Simultaneous dual-energy planar images were obtained at 5 min, 3 and 5 hr. All studies were concordantly either positive (8/11) or negative (3/11) by both radionuclides. Exact agreement for segmental uptake was 93%, 94% and 94% for 5-min, 3- and 5-hr images, respectively. Exact agreement for defect reversibility by 3 and 5 hr were 95% and 92%. The initial defect contrasts and myocardial-to-lung ratios were similar by both agents but myocardial-to-liver ratio was lower by [123I]MPDA at 5 min, which became similar to 201Tl at 5 hr. Normal percent myocardial clearances of both agents were comparable and significantly higher than those in defect zones. Thus [123I]MPDA is suitable for myocardial imaging and correlates closely with 201Tl for initial postexercise myocardial uptake and defect reversibility. Defect reversibility appears to result from differential myocardial clearance from normal and ischemic regions.