Pharmacologic stress with dipyridamole has provided useful diagnostic, as well as prognostic, information in patients undergoing thallium-201 myocardial perfusion imaging. With its ultrashort half-life and a potent and consistent vasodilator effect, adenosine may be the coronary vasodilator of choice with myocardial perfusion imaging. Fifty-one healthy subjects and 93 patients with suspected coronary artery disease constituted the study group. In this multicenter study the comparative safety and diagnostic efficacy of single-photon emission computed tomography (SPECT) thallium imaging during adenosine-induced coronary hyperemia was compared with exercise treadmill stress. There was a mean increase in heart rate of 37% and a mean decrease in diastolic blood pressure of 5% during the adenosine infusion of 140 micrograms/kg per min for 6 min. Adenosine infusion was well tolerated in 95% of the subjects. Side effects requiring intervention occurred in seven subjects (5%). None of the subjects experienced a life-threatening complication. The sensitivity, specificity and predictive accuracy for detection of coronary artery disease with use of quantitative analysis was 83%, 87% and 84% for adenosine SPECT and 82%, 80% and 81% for exercise SPECT studies, respectively. Most false negative results with adenosine, as well as exercise SPECT studies, occurred in patients with single-vessel disease. The first-order concordance (no defect vs. defect) and second-order concordance (no defect vs. irreversible vs. reversible defect) was 89% and 78% between the two studies, respectively. Thus, the results of adenosine SPECT imaging are highly concordant with exercise SPECT thallium imaging. Adenosine SPECT thallium imaging provides a safe and highly accurate imaging mode for the detection of coronary artery disease.