Previous studies have validated the 133Xenon (133Xe) method to assess regional myocardial blood flow and coronary flow reserve (CFR). Doppler FloWire (DFW) has been used recently for measuring CFR to assess the physiological significance of coronary stenosis. Data obtained by DFW has never been correlated to 133Xe. Our study compared data from DFW measurement of CFR to that obtained by 133Xe in 31 consecutive patients with variable coronary stenosis. Regional myocardial blood flow was measured by assessing the rate constants of 133Xe washout using multicrystal gamma camera after injection (20 millicuries) in the right or left coronary artery. CFR was assessed by measuring resting and hyperemic coronary blood flow by 133Xe and DFW using i.v. adenosine (140 mcg/k/min x 3 min). CFR was also measured by DFW giving intracoronary (i.c.) adenosine (12 microg in the right coronary, 18 microg in the left). In both methods--133Xe and DFW--coronary flow reserve was defined as the ratio of maximal hyperemic-to-baseline flow. DFW and 133Xe assessment of CFR correlated highly, whether adenosine was used i.c.(r=0.87; P=0.0001) or i.v.(r=0.78; P=0.0001). CFR obtained by DFW following i.c. and i.v. adenosine correlated well (r=0.79; P=0.0001). i.c. adenosine has fewer side effects. Both DFW and 133Xe are comparable in measuring CFR in humans.