Infusions of LSD or tryptamine increase heart rate, respiratory rate and pupillary diameter, facilitate the flexor reflex and evoke the stepping reflex in the chronic spinal dog. When LSD is administered twice daily in a dose of 15 mcg/kg subcutaneously, tolerance develops to these effects of LSD and cross tolerance to these effects of tryptamine. These observations support the concept that tryptamine and LSD have a common mode of action and the hypothesis that LSD exerts some of its pharmacologic effects by acting as an agonist at tryptamine receptors.