Laryngeal chemoreflex (LCR) responses elicited by fluid irrigation of the larynx have been described repeatedly in animals, whereas evidence for a similar reflex in human infants is extremely limited. Using nasopharyngeal catheters to instill small volumes of warm saline or water into the pharynx, we examined the incidence and characteristics of such a reflex in nine premature infants. Saline and water elicited the same pattern of responses, which frequently included swallows, central apnea, and airway obstruction and less commonly featured coughs, prolonged apnea, and arousal. With the exception of arousal, the incidence of these responses was significantly greater after delivery of water stimuli than after saline bolus administration. We therefore deduce chemoreceptor involvement in generation of these reflex responses and propose a laryngeal site for this sensory system, as in animals. Since greater potency of water compared with saline was demonstrable in all the infants studied, we further conclude that most preterm infants possess an upper airway chemoreflex.