Arterial spin labeling (ASL) in combination with NMR imaging is an in vivo technique that quantifies tissue perfusion in absolute values (ml blood ⅐ min Ϫ1 ⅐ g tissue Ϫ1 ) with high temporal (1-10 s) and spatial (0.1-3 mm) resolution. It uses the arterial water spins as endogenous freely diffusible markers of perfusion and, hence, is a totally noninvasive method. The technique has been successfully applied to quantify baseline perfusion in many organs, including the heart, in humans and animals, and results were validated by comparison with gold standards, PET and microspheres, respectively. Because of the high sampling rate of perfusion with ASL and the possibility that measurements could be obtained without harm over indefinite periods of time, the technique has the potential for use in functional investigations of microcirculation regulation and resistance artery control in vivo. We describe examples of the use of ASL to this end. With use of specific technological developments, ASL determination of perfusion can be coupled with simultaneous acquisitions of 1 H and 31 P NMR spectroscopy data. These protocols offer new possibilities whereby the microcirculatory control of cell oxygenation and high-energy phosphate metabolism can be explored.arterial spin labeling; imaging; microcirculation; perfusion AT FIRST SIGHT, NONINVASIVE in situ visualization of resistance artery lumen and wall is well beyond the technological limits of in vivo NMR imaging, which has detection limits of 0