The purpose of the present study is to prospectively compare myocardial perfusion imaging with rubidium-82 (82Rb) by positron emission tomography (PET) with thallium-201 (201Tl) imaging by single-photon emission tomography (SPECT) by recording both studies with a single dipyridamole handgrip stress, and reading both sets of images with the same display technique. In a series of 202 patients with previous coronary arteriography, the sensitivity, specificity, and accuracy of 82Rb PET were 93%, 78%, and 90% and for 201Tl SPECT 76%, 80%, and 77%, respectively. When 70 patients with previous therapeutic interventions were excluded, the remaining 132 patients showed a sensitivity, specificity, and accuracy of 95%, 82% and 92% for 82Rb PET and 79%, 76%, and 78% for 201Tl SPECT. The improved contrast resolution of PET resulted in markedly superior images and a more confident identification of defects.