1. In infants, promethazine has been implicated in the pathogenesis of sleep apnoea, apparent life threatening events (ALTE) and the Sudden Infant Death syndrome (SIDS). The aim of the present study was to investigate, in a neonatal animal, the effects of a commonly used promethazine-containing medication on airway protective mechanisms and cardiorespiratory reflexes following simulated gastro-oesophageal reflux (GER) to different levels in the oesophagus and pharynx. 2. Physiological and radiographic recordings were made in 21 naturally sleeping (controls) and 21 sedated (1.5 mg/kg, p.o., promethazine) piglets. On 3 consecutive days physiological recordings were made in all piglets during active sleep. Gastro-oesophageal reflux was simulated by the injection of boluses of 0.5 mL HCl, pH 2 or 3, or NaCl (0.9%) at 37 degrees C into the pharynx, upper or lower oesophagus. 3. In healthy neonatal piglets, minimal sedation with promethazine, which did not affect behaviour during wakefulness, revealed previously unreported findings during active sleep. 4. The most significant effects were observed following simulated GER to the pharynx, with no effect observed in the lower oesophagus. In sedated piglets, compared with naturally sleeping piglets, there was a significant reduction in swallowing (P < 0.01), delayed radiological clearance of fluid (P < 0.05), a reduction in breathing rate, oxygen saturation and heart rate and an increase in apnoea. 5. These findings are consistent with a low dose of promethazine producing a significant attenuation of airway protective mechanisms and, thus, stimulation of the laryngeal chemoreflex. The results suggest a mechanism for the association observed between promethazine use and the occurrence of ALTE and SIDS. The results support continued caution and suggest the need for greater regulation of promethazine-containing medications in infants.