Cooling-induced reduction of skin blood flow results from a reflex increase in sympathetic output and an enhanced vasoconstrictor activity of skin vessels. The latter has been proposed to be mediated by increased reactivity of α_2C-adrenoceptors during cooling in studies with isolated cutaneous vessels in vitro. We have previously shown in studies with tetrodotoxin-treated mice in vivo that reduction of plantar skin blood flow (PSBF) induced by local cooling results primarily from increased reactivity of α_2C-adrenoceptors. In addition, we showed that part of the cooling-induced response was also mediated by α₁-adrenoceptors. However, the mechanisms involved in the cooling-induced responses mediated by α₁-adrenoceptors have not been elucidated. The present study is an investigation seeking to clarify the mechanisms involving α₁-adrenoceptors. Medial plantar arteries were isolated from male ddY mice and changes in vessel diameter were measured in vitro using pressurized arteriography. In vivo measurements of PSBF were performed on artificially ventilated tetrodotoxin treated mice, anaesthetized with pentobarbital sodium, using laser Doppler flowmetry, with the probe positioned above the medial plantar artery. In the in vitro studies with isolated plantar arteries, cooling from 37 to 28°C did not affect the constrictor potency of phenylephrine, an α₁-adrenoceptor agonist, and the threshold concentration to evoke constriction was rather higher at 28°C than it was at 37°C. The cooling also suppressed the constrictor efficacy of UK14,304, an α₂-adrenoceptor agonist. In contrast, cooling the air temperature around the foot from 25 to 10°C in vivo decreased PSBF, which was significantly inhibited by phentolamine, an α-adrenoceptor antagonist, although MK-912, an α_2C-adrenoceptor antagonist, had no effect on it. These results suggest that although α₁-adrenoceptors are involved in cooling-induced reduction of PSBF in mice, the response is unlikely to result from an enhancement of α₁-adrenoceptor-mediated vasoconstriction of plantar arteries during cooling.