The effect of cold has been studied on isolated canine and human blood vessels. These have led to the following conclusions concerning the phenomenon of the hunting reaction seen in human extremities on their exposure to severe cold. (1) On exposure to cold there is a marked increase in the affinity of the postjunctional alpha-adrenoceptors for norepinephrine. This results in a powerful constriction of the blood vessels and a cessation of blood flow to the distal tissue. As the temperature of the tissues rapidly falls, sympathetic nerve conduction is interrupted and vasodilatation occurs, due to the cessation of norepinephrine release and the depressor action of cold on the contractile machinery. The resultant return of blood flow rewarms the tissue, nerve conduction is reestablished, and this combined with the increased affinity of the alpha-adrenoceptors for norepinephrine leads to renewed vasoconstriction. Repetition of this cycle could result in the hunting reaction. (2) There appears to be a difference between the cutaneous artery and vein, in that the latter remains constricted at lower temperatures. (3) Preliminary experiments suggest that the response of the human cutaneous vein to cold is qualitatively similar to the dog vein, although some quantitative differences are present.