Previous studies from our laboratory have demonstrated that altering muscle temperature of the exercising forearm can elicit changes in muscle sympathetic nerve activity (MSNA) during ischemic isometric handgrip. The purpose of the current study was to determine the interactive effect of muscle temperature and blood flow on MSNA responses during dynamic handgrip (DHG). Eight subjects performed 2 bouts of graded DHG to fatigue followed by 2 min of postexercise muscle ischemia (PEMI). Local heating of the forearm increased muscle temperature from 33.6±0.3 to 38.3±0.5°C (p < 0.05). Mean arterial pressure and heart rate increased in a linear fashion during graded DHG (p < 0.05), but were not affected by muscle temperature. MSNA (burst frequency and total activity) at fatigue and PEMI were elevated in all conditions (p < 0.05). However, MSNA responses were not different between temperature conditions. To ascertain the effect of blood flow, 8 additional subjects completed 2 trials of ischemic DHG under normothermic or warm conditions followed by 2 min of PEMI. MSNA, expressed as burst frequency and total activity, was significantly greater in warm compared to the normothermic trial (14 ± 3 and 9 ± 2 bursts/30s, and 1234 ± 260 and 751 ± 199 units/30s, respectively). This finding supports the concept that muscle heating sensitizes skeletal muscle afferents during muscle contractions and augments MSNA in humans. However, based on these findings, we conclude that muscle blood flow modulates the effect of muscle temperature on MSNA during exercise.