Piperidine is an endogenous active amine. Intravenous or intra-arterial administration of piperidine produced vasodilation in anesthetized dogs. The vasodilative effect of piperidine was inhibited by atropine (0.3 mg/kg, i.v.). In the hind limb perfusion experiment in anesthetized dogs, piperidine produced vasodilation, while it showed no vasorelaxing action in various isolated canine arterial strip preparations. These results suggest that the vasodilation caused by piperidine may be produced through activation of muscarinic receptors and that piperidine may act on smaller resistance blood vessels but not on large conductance vessels. In addition, pipecolic acid and N-methyl piperidine, the respective precursor amino acid and metabolite of piperidine, were almost inactive, but nipecotic acid was 1/4 to 1/10 times as active as piperidine as vasodilators. It is suggested that the non-substituted amine moiety of piperidine is very important for the manifestation of vasodilative activity and that piperidine might play a role in regulation of peripheral vascular circulation.