Prone 201Tl myocardial perfusion SPECT has been shown to improve left ventricular inferior wall counts compared to supine imaging, thus minimizing diaphragmatic attenuation. Prone SPECT quantitative normal limits were developed and prospectively applied to 36 patients who had coronary angiography. The prone imaging table used had a cut-out under cardiac area which increased the average myocardial counts by 10.7% compared to prone SPECT through the standard table. Overall specificity and sensitivity were 80% and 93%, respectively. For the right, left circumflex and left anterior descending coronary arteries, the specificities were 94%, 71%, and 94%; and sensitivities were 88%, 89% and 78%, respectively. The normalcy rate in 55 normal patients was 89%. Incidence and the severity of patients motion in 200 prone SPECT studies were compared to 200 supine SPECT studies. Mild and severe motion occurred in 12% and 4% of the supine studies and in only 3.5% and none of the prone studies, respectively. When compared to supine SPECT, prone SPECT had higher (p less than 0.01) regional counts/pixel in the inferior wall and septum, but required an average increase of 2.9 +/- 1.0 cm in camera to chest wall distance and resulted in a reduction of total myocardial counts. Prone SPECT provides an alternative approach for patients who cannot tolerate supine imaging. It should be considered when inferior wall defects on supine imaging pose a diagnostic dilemma and when motion on supine imaging necessitates repeat acquisition.