To investigate the role of sympathetic neurovascular reactivity in the gender differences of cutaneous, cold-induced vasomotor response, we compared direct (at the site of cooling) and indirect (at a site remote from the cooling site) response measured by laser Doppler (LD) flowmetry in 12 healthy males and 12 healthy females. The females underwent testing twice, once in the follicular and once in the luteal phase of the menstrual cycle. We measured LD flow before and during local cooling of one hand at 15°C. We found that local cooling evokes a significantly greater decrease in cutaneous LD flow in females than in males in direct as well as in indirect response conditions (p < 0.05). Comparing the response in females in the different phases of menstrual cycle, we obtained a significantly greater direct response to local cooling in the luteal phase than in the follicular phase (p < 0.05). In contrast, there was no menstrual-cycle-dependent difference in the indirect response to cold. The results of our study strongly indicate that sympathetic neural reactivity, as assessed by way of an indirect response to a cold stimulus, significantly contributes to gender differences in the response to local cooling. In contrast, the variation in microvascular responsiveness to cold exposure due to the menstrual cycle is most probably caused by local vascular mechanisms rather than by variation in sympathetic neural reactivity to local cooling.