Contractile activity of the descending colon of the anesthetized dog was monitored with strain gage force transducers. Nicotine and tyramine caused primarily a relaxation of the circular and longitudinal muscle. A secondary stimulation frequently followed the inhibition. Adrenalectomy partially antagonized the effects of nicotine. Xylocholine and reserpine petreatment reduced the early portion of the inhibitory response to nicotine. Hexamethonium or a combination of adrenalectomy with either xylocholine or reserpine pretreatment abolished the effects of nicotine. The effects of tyramine were antagonized by cocaine and reserpine-pretreatment. Tolazoline and propranolol (in combination) reduced the effects of both nicotine and tyramine. We conclude that both nicotine and tyramine relaxed the colon by releasing catecholamines. Nicotine caused release from the adrenal glands and adrenergic nerve endings; tyramine produced release from the adrenergic nerve endings. Nicotine Catecholamines Colonic motility Tyramine Gastrointestinal tract Strain gage force transducers * The study was supported by a grant from the American Medical Association, Education and Research Foundation. It represents a portion of a doctoral dissertation by N.W. Weisbrodt.