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This article examines the relationship between endothelial dysfunction and "small vessel disease." Newer technologies have facilitated the study of this issue. Using a Doppler wire and the intracoronary administration of acetylcholine and papaverine, a difference can be made between functional and chronic-trophic disturbances of the coronary reserve. Papaverine induces smooth muscle cell-mediated vasodilation, acetylcholine induces nitric oxide (NO)-mediated vasodilation. The data revealed that endothelial dysfunction may be related to disturbances in the microcirculation. In addition to those vasomotor-related properties, other factors such as antithrombotic, antiadhesive disturbances contribute to the disturbed microcirculation. Newer techniques, such as serial positron emission tomography, may yield an even better understanding of these processes.