The neural mechanisms of reactive cutaneous hyperaemia were studied by using a novel experimental approach: the simultaneous measurement of cutaneous blood flow by laser-Doppler flowmetry in adjacent innervated and chemodenervated skin regions of the rat hindpaw served by the same artery. Transient occlusion of the femoral artery (0.5-6 min) resulted in reactive hyperaemia that was greatly reduced in the chemodenervated region. After 3 min arterial occlusion, peak cutaneous blood flow was 109+/-13% vs. 53+/-7%* (% change from baseline, n=11, *P<0.05), and the total hyperaemic response was 110+/-21 vs. 52+/-12* (arbitrary perfusion units) in intact vs. chemodenervated skin regions, respectively. The findings provide clear evidence for the involvement of peptidergic capsaicin-sensitive afferent nerves in the mechanism of reactive cutaneous hyperaemia.