Serotonin challenge in the nose produces sneezing and rhinorrhoea. To study the mode of action of serotonin in the nose, 14 normal persons, in a double-blind, randomized study, were provoked with serotonin in three concentrations. Fifteen minutes before challenge, they were pretreated in the nose with either a cholinoceptor antagonist (atropine), a serotonin antagonist (methysergide), an H1-histamine antagonist (chlorpheniramine) or isotonic saline. The number of sneezes was noted, and the amount of secretions measured. Serotonin induced dose-related increase in sneezing and hypersecretion (P less than 0.02). Atropine pretreatment reduced the amount of secretion (P less than 0.05 and P less than 0.1), but had no effect on sneezing. Methysergide and chlorpheniramine had no effect on the serotonin-induced nasal symptoms. Unilateral challenge with serotonin induced secretions from both sides, suggesting that serotonin-induced nasal symptoms are partly reflex-mediated.