Nocturnal asthma has been associated with nighttime gastroesophageal reflux (GER). To establish whether the presence of acid in the lower esophagus causes bronchoconstriction, nine children with nocturnal asthma and GER underwent intraesophageal acid-infusion challenges during sleep. The patients were divided into two groups on the basis of presence or absence of a positive Bernstein test for esophagitis. The test was considered positive if acid infusion produced symptoms of heartburn. On two occasions, at approximately midnight and 4 to 5 A.M., 30 ml of normal saline was infused over 15 min into the distal esophagus followed by a similar infusion of 0.1N HCl. Respiration was continuously monitored by inductance plethysmography along with clinical evaluation. The saline and midnight acid infusions had no effect in either patient group; however, with the 4 to 5 A.M. acid infusion, all the patients with a positive Bernstein test developed significant changes in their respiratory pattern indicative of bronchoconstriction as well as overt clinical wheezing. In the patients with a negative Bernstein test, the 4 to 5 A.M. acid infusion had no effect. It is concluded that during sleep the presence of acid in the lower esophagus can trigger bronchoconstriction in asthmatic children with a positive Bernstein test and that these children appear to be more susceptible to the bronchoconstrictive effects of intraesophageal acid at 4 to 5 A.M. than at midnight.