Whether nitric oxide (NO) is involved in cutaneous active vasodilation during hyperthermia in humans is unclear. We tested for a role of NO in this process during heat stress (water-perfused suits) in seven healthy subjects. Two forearm sites were instrumented with intradermal microdialysis probes. One site was perfused with the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) dissolved in Ringer solution to abolish NO production. The other site was perfused with Ringer solution only. At those sites, skin blood flow (laser-Doppler flowmetry) and sweat rate were simultaneously and continuously monitored. Cutaneous vascular conductance, calculated from laser-Doppler flowmetry and mean arterial pressure, was normalized to maximal levels as achieved by perfusion with the NO donor nitroprusside through the microdialysis probes. Under normothermic conditions, L-NAME did not significantly reduce cutaneous vascular conductance. During hyperthermia, with skin temperature held at 38-38.5 degreesC, internal temperature rose from 36.66 +/- 0.10 to 37.34 +/- 0.06 degreesC (P < 0.01). Cutaneous vascular conductance at untreated sites increased from 12 +/- 2 to 44 +/- 5% of maximum, but only rose from 13 +/- 2 to 30 +/- 5% of maximum at L-NAME-treated sites (P < 0.05 between sites) during heat stress. L-NAME had no effect on sweat rate (P > 0.05). Thus cutaneous active vasodilation requires functional NO synthase to achieve full expression.