-Investigators report that local heat causes an increase in skin blood flow consisting of two phases. The first is solely sensory neural, and the second is nitric oxide mediated. We hypothesize that mechanisms behind these two phases are causally linked by shear stress. Because microvascular blood flow, endothelial shear stress, and vessel diameters cannot be measured in humans, bat wing arterioles (26.6 Ϯ 0.3, 42.0 Ϯ 0.4, and 58.7 Ϯ 2.2 m) were visualized noninvasively on a transparent heat plate via intravital microscopy. Increasing plate temperature from 25 to 37°C increased flow in all three arterial sizes (137.1 Ϯ 0.3, 251.9 Ϯ 0.5, and 184.3 Ϯ 0.6%) in a biphasic manner. With heat, diameter increased in large arterioles (n ϭ 6) by 8.7 Ϯ 0.03% within 6 min, medium arterioles (n ϭ 8) by 19.7 Ϯ 0.5% within 4 min, and small arterioles (n ϭ 8) by 31.6 Ϯ 2.2% in the first minute. Lidocaine (0.2 ml, 2% wt/vol) and N G -nitro-L-arginine methyl ester (0.2 ml, 1% wt/vol) were applied topically to arterioles (ϳ40 m) to block sensory nerves, modulate shear stress, and block nitric oxide generation. Local heat caused only a 10.4 Ϯ 5.5% increase in diameter with neural blockade (n ϭ 8) and only a 7.5 Ϯ 4.1% increase in diameter when flow was reduced (n ϭ 8), both significantly lower than control (P Ͻ 0.001). Diameter and flow increases were significantly reduced with N G -nitro-L-arginine methyl ester application (P Ͻ 0.05). Our novel thermoregulatory animal model illustrates 1) regulation of shear stress, 2) a nonneural component of the first phase, and 3) a shear-mediated second phase. The time course of dilation suggests that early dilation of small arterioles increases flow and enhances second-phase dilation of the large arterioles. nitric oxide; in vivo; shear stress HUMAN SKIN RESPONDS TO LOCAL temperature increases with a biphasic increase in skin blood flow (SkBF). Within the first few minutes after the local application of heat, SkBF reaches a peak and then begins to decline. Three to five minutes after heating, SkBF reaches a nadir and then increases once again (8,16,26). The second slower and more sustained response typically rises above the initial peak value. Typically, SkBF is measured noninvasively in human subjects using laser Doppler flowmetry (LDF), which ensures that the complex interaction of thermoregulatory mechanisms controlling vascular responses remains intact. The resulting behavior is ubiquitous and consistent (8,39). Investigators universally separate the response to local heat into two distinct phases (16,26).Investigators believe that these two phases are controlled by two mechanisms (26). When a local anesthetic is used to block sensory input, the first phase of the biphasic flow response is abolished, suggesting sensory neural-mediated microvascular dilation. The second phase is diminished with the addition of nitric oxide (NO) synthase (NOS) inhibitors (8,16,26), suggesting NO-dependent microvascular dilation. A direct link between the mechanisms of the neural-and NO-mediated increases in...