The purpose of this series of studies was to compare regional skin blood flow (SkBF) in adult humans. Forearm and calf skin sites were instrumented with microdialysis fibers, local skin heaters, and laser-Doppler probes in nine healthy volunteers. Baseline cutaneous vascular conductance (CVC) (laser-Doppler flow / blood pressure) was measured at a local skin temperature (Tloc) of 33 °C and 42 °C. All data are expressed as CVC. In study 1, forearm and calf sites were compared to determine if SkBF differed by region. Baseline CVC was higher in the calf than in the forearm (24±2 and 16±1 %max) (P=0.04). At a Tloc of 42 °C, initial peak CVC was higher in the forearms (78±3 %max) than the calf (63±3 %max) (P=0.004). Plateau phase CVC was higher in forearms (90±2 %max) than calves (98±1 %max) (P=0.008). In study 2, the role of nitric oxide synthase (NOS) in the cutaneous vasodilator response in the skin of the forearms and calves using the NOS inhibitor L-NAME was investigated. Baseline CVC between control and L-NAME treated sites was higher (27±2 vs 17± 1%max, respectively; P=0.04) for the calf, but did not differ (P=0.26) for forearms. At a Tloc of 42°C, CVC at forearm and calf L-NAME sites did not differ (P=0.45). In study 3, bretylium tosylate (BT) was used to examine the role of sympathetic nerves on regional SkBF. Baseline BT sites differed between the forearm and calf (P=0.04). Initial peak CVC for forearm sites treated with BT (62±3 %max) were lower than the calf sites (78±2 %max) (P=0.02). CVC achieved at arm and calf BT sites did not differ at plateau (P=0.28). We conclude that differences exist in regional SkBF control at rest (thermoneutral) and in response to local skin warming. Differences observed suggest that the NOS contribution to basal vascular tone was higher in calves than forearms and accounts for the higher basal SkBF and vasodilator response to a Tloc of 42 °C in the legs. Initial peak CVC in the calf treated with BT increased which may, in part, indicate increased vasoconstrictor tone.