The responses of strips of rabbit aorta to almost maximal doses of nicotine were less readily antagonized by five antisympathomimetic agents than were comparable responses to noradrenaline. The effect was most marked with dibenamine, ergotamine, and tolazoline: approximately twice the dose of noradrenaline was required to match the test dose of nicotine after treatment with the antagonists. Dose/response curves for nicotine before and after phentolamine 10(-7) indicate that the phenomenon may be reversed with low doses of nicotine and that the release of noradrenaline by nicotine within the tissues is probably a graded response. The pattern of nicotine/phentolamine antagonism in this preparation is consistent with the view that nicotine acts indirectly by releasing a noradrenaline-like substance, and the difficulty found in antagonizing responses to nicotine with antisympathomimetic agents is probably similar to that responsible for failure of atropine to block some parasympathomimetic responses to nicotine.