Analysis of post-contraction MRI signal intensity (SI) transients may allow noninvasive studies of microvascular reactivity and blood oxygenation recovery. The purpose of this study was to determine the physiological basis for post-contraction changes in short-echo (6 ms) and long-echo (46 ms) gradient-echo (GRE) MRI signals (S(6) and S(46), respectively). Six healthy subjects were studied with the use of dual GRE MRI and near-infrared spectroscopy (NIRS). S(6), S(46), total hemoglobin concentration ([THb]), and oxyhemoglobin saturation (%HbO(2)) were measured before, during, and after 2 and 8 s dorsiflexion maximal voluntary contractions, and 5 min of proximal arterial occlusion. The changes in S(6) and [THb] after the 2-s contractions were similar to those following 8-s contractions, but changes in %HbO(2) and S(46) were greater following 8-s contractions than after the 2-s contractions. [THb] and S(6) did not change during and following 5 min of arterial occlusion, but %HbO(2) and S(46) were both significantly depressed at similar occlusion durations. Also, distance measures indicated similarity between S(6) and [THb] and between S(46) and %HbO(2). We conclude that following brief human skeletal muscle contractions, changes in S(6) primarily reflect changes in blood volume and changes in S(46) primarily reflect changes in blood oxygenation.