The feasibility, safety and diagnostic accuracy of single photon emission computed tomography (SPECT) with thallium-201 imaging during adenosine-induced coronary hyperemia were evaluated in 53 patients with and 7 without coronary artery disease proved by coronary angiography. Adenosine was infused intravenously at a dose of 0.14 mg/kg body weight per min for 6 min and thallium was injected at 3 min. Adenosine caused an increase in heart rate (68 +/- 12 at baseline versus 87 +/- 18 beats/min at peak effect, p less than 0.0001) but no change in blood pressure. The sensitivity and specificity were 92% (95% confidence intervals 81% to 98%) and 100% (95% confidence intervals 59% to 100%), respectively; 20 (61%) of 33 patients with multivessel coronary artery disease were also correctly identified. In 30 patients, the predictive accuracy of adenosine thallium imaging was slightly higher than that of exercise SPECT thallium imaging (90% versus 80%, p = NS) (95% confidence intervals 72% to 97% and 61% to 92%, respectively). In 25 patients, two-dimensional echocardiography during adenosine infusion disclosed a new wall motion abnormality in 2 (10%) of 20 patients with coronary artery disease; 80% of these patients had reversible thallium defects (p less than 0.001). Side effects were mild and transient; aminophylline was used in only three patients. Thus, adenosine SPECT thallium imaging provides a high degree of accuracy in the diagnosis of coronary artery disease. The results are comparable with those of exercise SPECT thallium imaging. Most reversible defects in the adenosine study are not associated with any transient wall motion abnormality.