Hyperthermia is thought to increase limb tissue blood flow (BF) through activation of thermosensitive mechanisms within the limb vasculature (1). However, the precise vascular locus in which hyperthermia causes vasodilatation and increases in BF in the different segments of the human leg is not fully characterised and understood. Specifically, the distribution of upper- and lower-leg BF during local hyperthermia—the BF responses in the major leg arteries and microcirculation as a result of whole and partial limb hyperthermia—remain unknown. This study tested the hypothesis that temperature-sensitive mechanisms alter limb haemodynamics by acting downstream from the conduit arteries, whether that be whole-leg haemodynamics in response to whole-leg heating (WLH) or leg-segmental haemodynamics in response to upper- (ULH) or lower-leg heating (LLH), respectively. METHODS: A cohort of healthy males and females (31±13 years) participated in three protocols. Leg haemodynamics of the common (CFA), superficial (SFA) and profunda (PFA) femoral arteries and popliteal artery (POA), and temperature profiles of the experimental and control leg were measured during each protocol: (1) 3h of WLH followed by 3h of passive recovery (n=5); (2) 1h of ULH followed by 30min of cooling and a subsequent 1h bout of ULH (n=8); (3) 1h of LLH (n=6). RESULTS: WLH increased mean whole-leg temperature (TLeg) of the experimental leg by 4.2±1.2°C (mean±SD), whilst core and control-leg temperatures remained stable. WLH induced ≥3-fold increases in blood perfusion in CFA, SFA, PFA and POA of the experimental leg, whilst control leg haemodynamics remained stable. During WLH, upper-leg BF increased by 499±331 ml/min and lower-leg BF increased by 277±136 ml/min, in a linear response to whole TLeg (R2=.95; p<.01). When expressed in relation to limb segment tissue mass, however, upper- and lower-leg BF were similar: ~9 ml/min/100g. Following the cessation of WLH, BF remained higher in the experimental leg for the subsequent 3h. Furthermore, ULH increased upper TLeg by 3.3±0.9°C and upper-leg BF by 536±243 ml/min which are comparable to WLH, without any changes to lower TLeg tissue oxygenation or BF. Conversely, LLH increased lower TLeg and BF—5.7±0.9°C and 287±130 ml/min—without altering upper TLeg, tissue oxygenation or skin and PFA BF. DISCUSSION: The present findings demonstrate that WLH induces a sustained ≥3-fold elevation in upper- and lower-limb BF and that segmental hyperthermia matches the regional thermal hyperaemia without affecting BF, temperature or tissue oxygenation of the non-heated limb segment. These findings together with the unchanged BF in the PFA and POA during lower and upper leg heating, support the notion that local downstream thermosensitive mechanisms control human leg circulation during hyperthermia.