Muscle performance is markedly influenced by tissue perfusion. 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 et 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, T1 and T2 were measured in 14 subjects during rest, ischemia, and reactive hyperemia. Mean leg muscle T1 in healthy volunteers is 850 ms at rest and 834 ms at reperfusion, leading to a calculated reactive hyperemia flow increase (T1 flow) of 103 +/- 40 ml/100 ml/min. T1 flows correlate well with NMR-plethysmography values. Changes in T2, which are sensitive to both deoxyhemoglobin content and vessel diameter variations, are also correlated with perfusion measurements. T1 changes allow quantification of regional perfusion in human muscle during reactive hyperemia.