AbstractMuscle performance is markedly influenced by tissue perfu‐sion. Techniques that allow quantification of microvascular flow are limited by the use of ionizing radiation. In this investigation, we apply an NMR model previously developed by Detre ef al. to the measurement of human muscle perfusion during reactive hyperemia. We compare our results with conventional plethysmography adapted to NMR. Using echo‐planar imaging,T1andT2were measured in 14 subjects during rest, ischemia, and reactive hyperemia. Mean leg muscleT1in healthy volunteers is 850 ms at rest and 834 ms at reperfusion, leading to a calculated reactive hyperemia flow increase (T1flow) of 103 ± 40 ml/100 ml/min.T1flows correlate well with NMR‐plethysmography values. Changes inT2, which are sensitive to both deoxyhemoglobin content and vessel diameter variations, are also correlated with perfusion measurements.T1changes allow quantification of regional perfusion in human muscle during reactive hyp