Background-We hypothesized that coronary blood flow (CBF) reserve could be quantified noninvasively in humans using myocardial contrast echocardiography (MCE). Methods and Results-Eleven patients with normal epicardial coronary arteries (group I) and 19 with single-vessel coronary stenosis (group II) underwent quantitative coronary angiography, MCE, and CBF velocity measurements at rest and during intravenous adenosine infusion. In group I patients, MCE-derived myocardial blood flow (MBF) velocity reserve (2.4+/-0.08) was similar to CBF velocity reserve using a Doppler flow wire (2.4+/-1.1), Patients with a single risk factor had a significantly higher MBF reserve (3.0+/-0.89) than those with greater than or equal to2 risk factors (1.7+/-0.22). In group II patients, significant differences were found in MBF velocity reserve in patients with mild (<50%), moderate (50% to 75%), or severe (>75%) stenoses (2.2+/-0.40, 1.6+/-0.65, and 0.55+/-0.19, respectively; P=0.005). A linear relation was found between flow velocity reserve determined using the 2 methods (r=0.76, P<0.001), and a curvilinear relation was noted between the percent coronary stenosis measured using quantitative coronary angiography and velocity reserve using both methods. Conclusions-CBF reserve can be measured in humans using MCE. This method may allow the noninvasive assessment of coronary stenosis severity and the detection of microvascular dysfunction.