In humans, vasoactive intestinal peptide (VIP) may play a role in reflex cutaneous vasodilation during body heating. We tested the hypothesis that the NO-dependent contribution to active vasodilation is enhanced in the skin of subjects with CF, compensating for sparse levels of VIP. In two parallel protocols, microdialysis fibers were placed in the skin of 11 subjects with CF and 12 controls. Lactated Ringer's was perfused at one microdialysis site and N^G-nitro-L-arginine-methyl ester (2.7 mg·ml^-1; L-NAME) at a second microdialysis site. Skin blood flow was monitored with laser-Doppler flowmetry. In protocol 1, local skin temperature was increased 0.5°C every 5 sec to 42°C, then maintained at 42°C for ~45 min. In protocol 2, subjects wore a tube lined suit perfused with water at 50°C, sufficient to increase oral temperature (T_or) 0.8°C. Cutaneous vascular conductance (CVC) was calculated (flux/mean arterial pressure) and scaled as percent maximal CVC (sodium nitroprusside; 8.3 mg·ml^-1). Vasodilation to local heating was similar between groups. The change (CVC_max) in CVC with NO synthase inhibition on the peak (9±3 vs. 12±5%CVC_max;P=0.6) and the plateau (45±3 vs. 35±5%CVC_max;P=0.1) phase of the skin blood flow response to local heating was similar in CF subjects and controls respectively. Reflex cutaneous vasodilation increased CVC in CF subjects (58±4%CVC_max) and controls (53±4%CVC_max;P=0.37). NO synthase inhibition attenuated CVC in subjects with CF (37±6%CVC_max) and controls (35±5%CVC_max;P=0.8) to a similar degree. Thus, the preservation of cutaneous active vasodilation in subjects with CF is not associated with an enhanced NO-dependent vasodilation to preserve cutaneous active vasodilation.