Skin blood flow (SkBF) in humans is controlled by a noradrenergic active vasoconstrictor system and an active vasodilator system of an uncertain neurotransmitter. Understanding how these systems interact would be aided if the vasodilator system could be studied in the absence of effects of the vasoconstrictor system. To accomplish this we combined laser-Doppler velocimetry (LDV) with the local iontophoresis of bretylium in 10 studies with eight healthy subjects. Each subject had two forearm sites (0.64 cm2) treated with bretylium to block local norepinephrine release. LDV was monitored at those sites and at two untreated sites during 3-4 min of cold stress, 35-45 min of heat stress, and a final cold stress to verify blockade. In five studies, local temperature was raised to 39 degrees C at the LDV sites before the final cold stress. Whole body skin temperature was controlled by water-perfused suits. Mean arterial pressure (MAP) was measured noninvasively. Heart rate and internal temperature were also recorded. Cutaneous vascular conductance (CVC) was calculated as LDV/MAP. During the initial cold stress, performed 130 min after bretylium treatment, CVC at treated sites fell by an average of 0.3 +/- 3.2% (P greater than 0.10) and at untreated sites by 29.2 +/- 4.1% (P less than 0.001 between sites). During heat stress, CVC at treated sites rose by 419 +/- 66% and at control sites, by 517 +/- 90% (P greater than 0.10 between sites). The internal temperature threshold for cutaneous vasodilation was not statistically different between sites (P greater than 0.10).(ABSTRACT TRUNCATED AT 250 WORDS)