With use of invasive methods, coronary endothelial function is generally studied by examining the response of epicardial coronary arteries to intracoronary administered acetylcholine or to cold pressor testing. Because invasive methods have substantial inherent limitations, studies should attempt to evaluate coronary endothelial function noninvasively. This study examines a noninvasive technique for endothelium-related coronary stress testing. In myocardial regions supplied by nonstenotic coronary arteries, we compared positron emission tomography (PET) myocardial perfusion imaging with intracoronary Doppler flow velocity measurements during endothelium-related stress testing. PET perfusion was examined at rest and during cold pressor testing in 10 patients with 1-vessel coronary artery disease. In nonstenotic coronary arteries, flow velocity measurements were obtained at rest, during cold pressor testing, and during intracoronary administered acetylcholine. Perfusion and flow velocity responses and stress/rest ratios were compared between the techniques during the various circumstances. Positive correlations were found between: (1) cold pressor Doppler flow velocity responses and acetylcholine Doppler flow velocity responses (r = 0.84, SEE = 0.19, p = 0.003); (2) cold pressor PET perfusion responses and cold pressor Doppler flow velocity responses (r = 0.70, SEE = 0.17, p = 0.02); and (3) cold pressor PET perfusion responses and acetylcholine Doppler flow velocity responses (r = 0.62, SEE = 0.19, p = 0.05). These results suggest that in angiographically normal coronary arteries, both the flow velocity and the perfusion responses during cold pressor testing may be related to the response to acetylcholine.