Goat isolated trachea contracted in response to carbachol, histamine and 2‐pyridylethylamine (an H1‐receptor agonist) and relaxed after application of isoprenaline, 5‐hydroxytryptamine (5‐HT) and phenylephrine. Mepyramine, a selective H1‐receptor antagonist, blocked histamine‐ and 2‐pyridylethylamine‐induced contractions. In high doses it also exhibited some nonspecific antagonism to carbachol. After H1‐receptor blockade, 4‐methylhistamine and dimaprit (specific H2‐agonists) relaxed the carbachol‐contracted trachea. Propranolol, a β‐adrenoceptor blocker, antagonized relaxation in response to isoprenaline and phenylephrine. In high doses, it produced a reversal of the phenylephrine response. Indomethacin enhanced contractions in response to carbachol and histamine. Relaxation to 5‐HT was not affected by propranolol, indomethacin, metiamide or cimetidine (H2‐blockers). These findings appear to exclude the involvement of adrenergic, prostaglandinergic and H2‐histaminergic mechanisms in the mediation of this response. Atropine potentiated 5‐HT‐induced relaxations. This suggests the participation of a ‘masked’ excitatory cholinergic mechanism. Methysergide, dibenamine and dibenzyline selectively antagonized or reversed 5‐HT‐induced relaxation. Dibenamine and dibenzyline enhanced relaxations to isoprenaline. This investigation showed (i) a relaxant response of goat trachea to 5‐HT, mediated via D‐muscular tryptamine receptors; (ii) a small population of excitatory M‐neuronal tryptamine and α‐adrenoceptors; and (iii) predominance of H1‐histamine receptors in the goat trachea. 1979 British Pharmacological Society