Background The physiological assessment of angiographically intermediate-severity stenoses remains problematic. Functional measurements of poststenotic intracoronary Doppler coronary flow reserve can be performed in humans but have not been correlated with hyperemic myocardial perfusion imaging or angiographic data in this patient population. Methods and Results Thirty-three patients undergoing diagnostic quantitative coronary angiography (QCA) for assessment of intermediate-severity coronary artery disease (mean QCA percent diameter stenosis, 56+/-14%) were studied. Proximal and distal poststenotic Doppler coronary flow velocities were measured (left anterior descending coronary artery, 16; right coronary artery, 10; left circumflex artery, 7 patients) before and during peak maximal hyperemia with intracoronary adenosine (8 to 12 mu g). Intravenous pharmacological stress (adenosine, 20 patients; dipyridamole, 13 patients) Tc-99m-sestamibi tomographic perfusion imaging was performed within 1 week of coronary flow-velocity studies. kappa statistics were calculated to measure the strength of correlation among coronary flow velocities, perfusion imaging data, and QCA results. QCA stenosis severity (abnormal, greater than or equal to 50% diameter stenosis) and poststenotic Doppler coronary flow reserve (ratio of abnormal distal hyperemic to basal flow, less than or equal to 2.0) were correctly correlated in 20 of 27 patients (74%; kappa=.48). QCA stenosis severity and Tc-99m-sestamibi imaging (abnormal if one or more reversible myocardial segments were present in the poststenotic zone) were correlated in 28 of 33 patients (85%; kappa=.63). Tc-99m-sestamibi imaging results agreed with the basal (nonhyperemic) proximal-to-distal velocity ratio (normal, <1.7) in 15 of 31 patients (48%; kappa=.17). The strongest correlation occurred between hyperemic distal flow-velocity ratio measurements and Tc-99m-sestamibi perfusion imaging results in 24 of 27 patients (89%; kappa=.78). All 14 patients with abnormal distal hyperemic flow-velocity values had corresponding reversible Tc-99m-sestamibi tomographic defects. More reversibly hypoperfused segments were present in patients with abnormal poststenotic hyperemic flow-velocity ratios (abnormal, 2.4+/-0.7 segments; normal, 0.6+/-1.0 segments; P<.05). The number of poststenotic myocardial Tc-99m-sestamibi perfusion defects was correlated with the QCA percent cross-sectional area reduction (P<.02) and with minimal luminal diameter (P<.05) of intermediate-severity coronary artery stenoses. Conclusions Two technologically diverse functional measures of stenosis severity - Doppler-derived poststenotic hyperemic intracoronary flow reserve and vasodilator stress Tc-99m-sestamibi myocardial perfusion imaging - are highly (89%) correlated. The physiological assessment of coronary stenoses of angiographically intermediate severity may be improved by the use of these techniques.