The laryngeal chemoreflex (LCR) consists of apnea, laryngospasm, and cardiovascular changes in neonates after laryngeal irritation and has been implicated in sudden infant death syndrome and pnea of infancy. Antihistamines attenuate a similar vagally mediated pulmonary chemoreflex. The ntravenous antihistamine effect on the LCR was studied in neonatal piglets. Laryngeal muscle activity, espiration, blood pressure, and pulse were measured during water stimulation of the LCR. After aseline LCR recordings, intravenous diphenhydramine (2.5 mg/kg) or cimetidine (20 mg/kg) was olused (control group received saline). LCR measurements were repeated over 7 hours. Diphenhydramine ignificantly shortened apneas (P<.05) 3 to 7 hours after drug bolus, which is believed to be secondary to entral atropinic effects. Cimetidine demonstrated no attenuation of the LCR.