We investigated the role of nitric oxide synthase (NOS) on regional cutaneous vascular function at rest (thermoneutral conditions) and during the vasodilator response to increased local skin temperature (Tloc). Dorsal forearm and lateral leg sites were instrumented with microdialysis fibers, local heaters, and laser-Doppler probes. All sites were heated from 33 °C to 42 °C. Each limb had 1 skin site treated with l-NAME to inhibit NOS, and 1 site infused with lactated Ringer's to serve as a control. Basal cutaneous vascular conductance (CVC) was measured at 33 °C, forearm sites averaged 14 ± 1%max and 17 ± 1%max at l-NAME and control sites, respectively (P = 0.26). CVC sites in the leg were different between l-NAME (17 ± 1%max) and control (27 ± 2%max) (P = 0.04). CVC between the forearm and the leg across control sites differed (P < 0.05). In contrast, at l-NAME treated sites, there was no difference between the forearm and leg sites (P = 0.23). When Tloc was increased to 42 °C, CVC at the control sites differed between the forearm 93 ± 1%max and leg 98 ± 1%max (P = 0.02). There were no differences between the arm and leg at l-NAME treated sites at 42 °C (P = 0.45). The findings of the current study were that the contribution of nitric oxide (NO) to the vasodilator response to an elevated Tloc is consistent between the arm and the leg, and, under thermoneutral conditions (33 °C), NO plays a larger role in the basal vascular function in the legs than that of the forearm. Accordingly, these data suggest, in part, that the differences in basal CVC between the forearm and leg are due to NOS activity.