NEW FINDINGS: What is the central question of this study? Temperature-sensitive mechanisms are thought to contribute to blood-flow regulation, but the relationship between exercising and non-exercising limb perfusion and blood temperature is not established. What is the main finding and its importance? The close coupling among perfusion, blood temperature and aerobic metabolism in exercising and non-exercising extremities across different exercise modalities and activity levels and the tight association between limb vasodilatation and increases in plasma ATP suggest that both temperature- and metabolism-sensitive mechanisms are important for the control of human limb perfusion, possibly by activating ATP release from the erythrocytes. 
Temperature-sensitive mechanisms may contribute to blood-flow regulation, but the influence of temperature on perfusion to exercising and non-exercising human limbs is not established. Blood temperature (T_B), blood flow and oxygen uptake (V̇_O2) in the legs and arms were measured in 16 healthy humans during 90 min of leg and arm exercise and during exhaustive incremental leg or arm exercise. During prolonged exercise, leg blood flow (LBF) was fourfold higher than arm blood flow (ABF) in association with higher T_B and limb V̇_O2. Leg and arm vascular conductance during exercise compared with rest was related closely to T_B (r² = 0.91; P < 0.05), plasma ATP (r² = 0.94; P < 0.05) and limb V̇_O2 (r² = 0.99; P < 0.05). During incremental leg exercise, LBF increased in association with elevations in T_B and limb V̇_O2, whereas ABF, arm T_B and V̇_O2 remained largely unchanged. During incremental arm exercise, both ABF and LBF increased in relationship to similar increases in V̇_O2. In 12 trained males, increases in femoral T_B and LBF during incremental leg exercise were mirrored by similar pulmonary artery T_B and cardiac output dynamics, suggesting that processes in active limbs dominate central temperature and perfusion responses. The present data reveal a close coupling among perfusion, T_B and aerobic metabolism in exercising and non-exercising extremities and a tight association between limb vasodilatation and increases in plasma ATP. These findings suggest that temperature and V̇_O2 contribute to the regulation of limb perfusion through control of intravascular ATP.