To determine the frequency of true myocardial ischemia caused by hemodynamic, metabolic, and regional functional abnormalities after intravenous adenosine infusion in patients with coronary artery disease, 13 patients--11 with coronary artery disease--received intravenous adenosine and thallium 201 during cardiac catheterization. Intracoronary adenosine levels increased by an average of 9.4-fold over baseline. Of the 11 patients, all had > or = 70% stenoses with a mean number of redistribution defects per patient of 3.3 +/- 0.7. Only two (18%) patients had new wall motion abnormalities detected by echocardiography during adenosine infusion. Pulmonary capillary wedge pressure did not significantly rise (13 +/- 7 to 17 +/- 8 mm Hg, p= NS). Lactate production occurred in two patients. Coronary sinus oxygen saturation levels rose from 29% +/- 6% to 68% +/- 8%, consistent with less myocardial oxygen extraction. Thus, despite a high prevalence of defects detected by 201Tl, the prevalence of true myocardial ischemia in patients with coronary artery disease undergoing pharmacologic stress imaging with intravenous adenosine is low. Perfusion defects induced by vasodilator stress are predominantly caused by heterogeneity of flow reserve rather than true ischemia.