In humans, heat stress increases cardiac output (Q) at rest and during exercise, in response to an enlarged thermoregulatory demand from the skin circulation (González-Alonso et al. 2008). It remains unclear whether heat stress causes muscle vasodilation and ergo whether muscle perfusion increases. This study tested the hypothesis that local leg and systemic hyperthermia increases leg muscle and systemic perfusion at rest and during exercise. We measured leg and systemic hemodynamics, O₂ transport and VO₂ at rest and during 6-min of one-legged knee-extensor exercise (25±3 W) in 7 active males (21±2 yr) in 4 conditions, in which participants’ hydration status was maintained: 1) control (Tcore ~37°C, Tskin ~33°C), 2) skin hyperthermia (Tc ~37°C, Tsk ~36°C), 3) skin and mild core hyperthermia (Tc ~38°C, Tsk ~37°C), and 4) high skin and core hyperthermia (Tc ~39°C, Tsk ~37°C). Femoral artery blood flow (LBF; Doppler ultrasound), thigh skin blood flow (SkBF; laser Doppler flowmetry) and blood gas and haematological variables (ABL 825, Radiometer) were measured in each condition. Data were analysed using a one-way ANOVA with repeated measures and appropriate post hoc analysis with significance accepted at P≤0.05. Data represent mean±SEM. At rest and during exercise, LBF and Q increased with each elevation in heat stress compared to control (peak delta LBF= 1.1±0.1 and 0.9±0.2 l min^-1 from baselines of 0.5±0.1 and 2.4±0.2 l min^-1, respectively; peak delta Q= 4.0±0.2 and 3.1±0.3 l min^-1 from baselines of 5.1±0.2 and 7.4±0.4 l min^-1, respectively). However, the increase in LBF and Q due to exercise (exercise hyperemia) was the same (~1.6 l min^-1) in all heat stress conditions. As expected SkBF increased with skin hyperthermia and the skin and mild core hyperthermia conditions (8.5±1.4-fold) but did not show a further increase with the high skin and core hyperthermia condition. The further increase in LBF was accounted for by an increased muscle perfusion. Additionally, the magnitude of the increase in SkBF with exercise during heat stress was the same in all conditions. Despite leg vascular conductance increasing with heat stress, MAP and perfusion pressure declined thereby suggesting that local vasodilation was responsible for the increase in leg perfusion. The elevation in leg muscle and skin temperature alone accounted for >50% of the increase in LBF and SkBF with high skin and core hyperthermia. The increase in LBF with each level of heat stress was followed by a decline in leg O₂ extraction. In line with this, leg VO₂ remained unchanged at rest and during exercise. The results suggest that leg muscle and skin blood flow increase with heat stress in resting and exercising humans. Furthermore, increases in muscle tissue temperature per se may contribute to the regulation of muscle blood flow and exercise hyperemia.