To compare stress/rest technetium 99m methoxy isobutyl isonitrile (Tc-MIBI) with stress redistribution thallium 201(T1-201) myocardial perfusion imaging, 36 patients were studied by single photon emission computerized tomography (SPECT) and planar methods. For SPECT, overall sensitivities for identification of patients with coronary artery disease were 93% ( 14 15) by Tc-MIBI and 80% ( 12 15) by Tl-201 (p = NS). For planar methods, overall sensitivities were 73% ( 11 15) by both Tl-201 and Tc-MIBI. Overall specificity was 75% ( 3 4 patients with normal coronary arteries) for both tracers with SPECT and Tc-MIBI by planar imaging and was 50% for planar TI-201 (p = NS). The normalcy rates for overall identification of coronary artery disease were determined in 17 patients with a low likelihood of disease. For SPECT, normalcy rates were 100% by Tc-MIBI and 77% by Tl-201 (p = NS). For planar, they were 94% by Tc-MIBI and 88% by Tl-201 (p = NS). Vessel sensitivities in the 35 stenosed coronary arteries (≥50% stenosis) for SPECT were 87% by Tc-MIBI and 77% by Tl-201 (p = NS). For planar, the vessel sensitivities were 60% by Tc-MIBI and 54% by Tl-201 (p = NS). For both tracers, the SPECT vessel sensitivities were significantly higher (p < 0.005) than planar vessel sensitivities. The vessel specificities in 22 coronary vessels with <50% stenosis were 86% by SPECT Tc-MIBI and Tl-201, 80% by planar Tc-MIBI and 73% by planar Tl-201 (p = NS, SPECT vs planar, Tc-MIBI vs Tl-201). Regarding myocardial segmental agreement, for the presence of stress defects the agreement was 91% for the 720 SPECT segments and 95% for the 540 planar segments. For severity of stress defects based on semiquantitative visual scoring, the exact agreement was 87% for SPECT and 80% for planar. For the pattern of reversibility in myocardial segments with stress defects, the agreement was 97% for SPECT and 91% for planar. This study demonstrated that Tc-MIBI and Tl-201 correlate well on both planar and SPECT images with respect to the identification of patients with coronary artery disease, identification of disease in individual coronary arteries, the presence and severity of perfusion defects, and the assessment of defect reversibility. Futhermore, SPECT Tc-MIBI was shown to be superior to planar Tc-MIBI for the identification of individual diseased vessels.