Doppler guidewire enables us to measure phasic coronary velocity and has been used for the measurement of coronary flow reserve (CFR). Although CFR is usually calculated by the quotient of peak flow velocity during papaverine infusion and flow velocity at rest, this assumption is true only if conduit vessel size is constant. To determine the accuracy of measurement of CFR using average peak velocity (APV) with Doppler guidewire, we investigated the influence of intracoronary papaverine on coronary flow velocity and coronary arterial diameter (CAD) and examined the correlation between CFR derived using APV and that derived using coronary blood flow (CBF) in 26 patients with normal coronary arteries. We measured phasic coronary flow velocity, and performed quantitative coronary angiography in the proximal left coronary artery at control and during 10 mg of intracoronary papaverine. Compared to control value, papaverine induced a significant increase in APV (% increase: 182 +/- 101%; P < 0.001). Papaverine also significantly increased CAD (16 +/- 10%; P < 0.001). Thus, CFR derived from APV was significantly lower than that derived from CBF (2.8 +/- 1.0 vs. 4.0 +/- 1.5, P < 0.001). Although there was a significantly strong positive correlation between these two methods (R2 = 0.83, P < 0.001), there was also considerable variability with regard to predicting one variable from the other. These results suggest the importance of standardizing the conditions in which coronary flow velocity is measured with regard to either controlling or measuring changes in epicardial coronary arterial diameter during changes in distal resistance vessel tone.