The clinical feasibility and usefulness of adenosine triphosphate-2Na (ATP) stress echocardiography for the detection of coronary artery disease (CAD) were assessed. Two-dimensional echocardiography and thallium-201 single photon emission computed tomography (SPECT) during ATP infusion were performed simultaneously in 58 consecutive patients (41 men and 17 women; mean age 66 +/- 12 years) with suspected CAD. ATP was infused intravenously at 0.16 mg/kg/min for 5 min and thallium was injected at 4 min. All patients underwent coronary angiography within 2 weeks of ATP echocardiography and ATP SPECT. An ischemic response during ATP infusion was detected by echocardiography as the development or worsening of a wall motion abnormality compared with the baseline and by SPECT as a perfusion defect that filled totally or partially during redistribution. Significant coronary artery stenosis was defined as > or = 75% diameter stenosis in a major epicardial vessel. The severity of the stenosis was classified as follows: Group A, lesions with significant coronary artery stenosis (> or = 75%, < 90%); Group B, lesions with severe coronary artery stenosis (> or = 90%) without collateral circulation; Group C, lesions with severe coronary artery stenosis (> or = 90%) with collateral circulation. Significant CAD was present in 43 of 58 patients. The overall sensitivity, specificity and accuracy of ATP echocardiography for detecting significant CAD were 70%, 100% and 78%, respectively, and those of ATP SPECT were 98%, 87% and 95%, respectively. In patients without previous myocardial infarction, the sensitivity of ATP echocardiography was 67%. The sensitivity of ATP echocardiography and ATP SPECT for detecting myocardial ischemia were 59% and 95% in patients with 1-vessel disease, 75% and 100% in those with 2-vessel disease, and 88% and 100% in those with 3-vessel disease, respectively. The induction of wall motion abnormality by ATP echocardiography was highly concordant with ATP SPECT imaging in patients with multivessel disease. Although the sensitivity of ATP echocardiography improved in patients with multivessel disease more than in those with single-vessel disease, detection of all diseased vessels was achieved in only 10% of patients with multivessel disease. The sensitivity of ATP echocardiography and ATP SPECT for detecting myocardial ischemia in individual vessels were: right coronary artery, 58% and 74%; left anterior descending artery, 59% and 97%; left circumflex artery, 27% and 68%. ATP-induced transient perfusion defects were associated with transient wall motion abnormality in only 57% of segments. The sensitivity of ATP echocardiography and ATP SPECT for detecting myocardial ischemia in patients with severe coronary stenosis were: Group A, 32% and 66%; Group B, 60% and 93%; Group C, 80% and 95%. The sensitivity of ATP echocardiography was significantly higher in the lesions with collateral circulation than in those without collateral circulation. ATP stress echocardiography is useful for detecting myocardial ischemia in patients with multivessel disease and in patients with severe coronary artery stenosis (> or = 90%). In particular, transient wall motion abnormality tends to be detected in the segments perfused by collateral circulation.