Nicotine affects the regulation of skin blood flow (SkBF), but the mechanisms involved are not well understood. We tested the hypothesis that acute exposure to nicotine inhibits both the initial neurally-mediated component and the later sustained component of SkBF responses to local heating of non-glabrous skin in humans. SkBF (measured by laser Doppler) responses to local heating of forearm skin from 32 to 42 °C were measured in 11 chronic smokers. Heating occurred at one site over 15 min (RAMP) and over 90 s (STEP) at another site, and was maintained for an additional 30 min. STEP heating was also applied to a site pretreated with bretylium via iontophoresis to inhibit noradrenergic neurotransmission. Responses were measured before and after acute administration of nicotine via cigarettes or nasal spray in two experimental sessions. Nicotine decreased resting skin blood flow (p<0.05); this response was inhibited by bretylium. During RAMP, nicotine increased the initial SkBF at 42°C (by ~12%, p<0.05). For STEP, nicotine increased the initial peak response (by ~25%, p<0.05), and decreased the sustained plateau value (by ~10%, p<0.05). In skin pretreated with bretylium, the increase caused by nicotine in the initial peak value persisted, but the plateau value was not different from pre-nicotine. These data suggest that in abstinent cigarette smokers, nicotine augments initial responses to both gradual and rapid non-painful heating of non-glabrous skin by sensitizing the sensory nerves that mediate the axon reflex associated with rapid vasodilation. In contrast, nicotine decreases SkBF responses to prolonged heating by activating noradrenergic nerves.