Objectives, The purpose of this study was to compare measures of coronary how reserve by an intracoronary Doppler guide wire with results of stress single-photon emission computed tomographic (SPECT) thallium-201 imaging in patients with intermediate coronary artery disease (40% to 70% stenosis). Background. Visual assessment of the coronary arteriogram as a means of predicting the physiologic significance of intermediate coronary stenoses is inaccurate. Coronary how reserve is a reliable marker of the functional importance of a coronary lesion. The recent development of an intracoronary Doppler guide wire permits routine assessment of coronary how reserve distal to coronary artery stenoses. Methods. We prospectively evaluated coronary flow reserve in 30 subjects with intermediate stenoses using an intracoronary Doppler guide wire during elective coronary angiography. Patients subsequently underwent stress SPECT thallium-201 testing, and the blinded interpretations were correlated. Coronary flow reserve in a control group with normal coronary arteries classified our sample into group 1 (abnormal flow reserve, <2.0) and group 2 (normal flow reserve, greater than or equal to 2.0). Results. As defined, the coronary flow reserve of 16 vessels in group 1 was diminished in comparison to that of 19 vessels in group 2 (p = 0.0001). Qualitative and quantitative analysis of stress SPECT thallium-201 images confirmed perfusion defects in 15 of 16 vascular territories in group 1 in contrast to 1 of 19 regions in group 2, The sensitivity, specificity and overall predictive accuracy of Doppler-determined coronary flow reserve for stress SPECT thallium 201 results were 94%, 95% and 94%, respectively. Conclusions. In appropriately selected patients with intermediate coronary artery stenoses, Doppler guide wire determination of lesion significance provides equivalent data to those acquired by stress SPECT thallium-201 imaging.