OBJECTIVE The reduction of skin blood flow induced by local cooling results from a reflex increase in sympathetic output and an enhanced vasoconstrictor activity of cutaneous vessels. The present study investigated the latter local response in vivo in tetrodotoxin-treated mice, in which the sympathetic nerve tone was abolished. METHODS Male ddY mice, anaesthetized with pentobarbitone, were treated with tetrodotoxin and artificially ventilated. The plantar skin blood flow (PSBF) was measured by laser Doppler flowmetry. RESULTS Cooling the air temperature around the left foot from 25 to 10 degrees C decreased the PSBF of the left foot. Bunazosin, an alpha (1)-adrenoceptor antagonist, RS79948, an alpha (2)-adrenoceptor antagonist, and MK-912, an alpha (2C)-adrenoceptor antagonist, all significantly inhibited the cooling-induced reduction of PSBF; the inhibition by bunazosin was relatively small compared with that by RS79948 and MK-912. The response was not affected by guanethidine or bretylium, but was diminished in adrenalectomized mice. An intra-arterial injection of clonidine, an alpha (2)-adrenoceptor agonist, to the left iliac artery of adrenalectomized mice caused a transient decrease in PSBF, which was significantly augmented at 10 degrees C. MK-912 suppressed only the augmented portion at 10 degrees C. Y-27632, H-1152 and fasudil, Rho kinase inhibitors, also inhibited the cooling-induced reduction of PSBF. RS79948 caused no further reduction of the cooling-induced response after the inhibition by Y-27632. CONCLUSIONS Local cooling-induced reduction of skin blood flow in mice primarily results from increased reactivity of alpha (2C)-adrenoceptors to circulating catecholamines, in which the Rho/Rho kinase pathway is involved.