The isolated tail artery when exposed to 0.14-2.80 microM tityustoxin (a purified peptide from the venom of the scorpion Tityus serrulatus) underwent a transient contraction which was followed by a long lasting period of unresponsiveness to further additions of the toxin. Reserpine pretreatment, the addition of phentolamine, tetrodotoxin, verapamil or lowering the sodium concentration abolished the responses to the toxin. Cocaine potentiated it. Tityustoxin caused a slight leftward shift of the dose-response curves to adrenaline and norepinephrine and a large potentiation of the frequency-response curves to electrical stimulation. The latter effect was greater within the lower range of frequencies assayed, which coincide with those of the physiological discharge of sympathetic nerves. These data indicate that in the tail artery the tityustoxin acts indirectly on the smooth muscle through the release of endogenous catecholamines. Most likely, changes of the properties of the sodium channels and calcium influx are involved in this effect at the nerve endings. The potentiation of the frequency-response curves suggests that the arterial hypertension produced by the scorpion sting may result mainly from an abnormally elevated overflow of sympathetic transmitters.