The association of gastroesophageal reflux and its sequelae in the infant with cystic fibrosis has gone virtually unnoticed. Eight of 40 newly diagnosed infants with cystic fibrosis seen over a 24 month period had significant gastroesophageal reflux, characterized by vomiting (7 infants), recurrent pneumonia (7 infants), and failure to thrive (4 infants). Gastroesophageal reflux was demonstrated by a combination of barium swallow, scintiscan, manometry, and esophagoscopy. Three infants had rapid and permanent alleviation of symptoms after standard medical therapy; in five infants, therapy failed and they required a Nissen fundoplication. Three infants required postoperative ventilatory support for 1, 2, and 5 days. No tracheostomies were required. Postoperative hospital stay averaged 12 days (range 5 to 30 days). There were no complications or perioperative deaths. All children had complete relief of their preoperative symptoms. The group that required surgery presented earlier (mean 7 weeks of age) to the cystic fibrosis center than either the medically treated group (mean 5 months of age) or the group free of gastroesophageal reflux symptoms (5 1/2 months of age). Also, postoperative hospitalization time markedly decreased from 50 percent of 577 combined patient days preoperatively to 4 percent of 1,639 days postoperatively; this 4 percent then paralleled what was seen in the group without gastroesophageal reflux (3 percent of 19,966 combined patient days) and the group controlled medically (5 percent of 1,897 days). The pulmonary manifestations of cystic fibrosis are extremely variable, and evaluation of the effect that any intervention has on the natural history of the disease is difficult. Nonetheless, we believe that even this small series suggests that gastroesophageal reflux and its complications can significantly alter the courses of some children with cystic fibrosis. Gastroesophageal reflux should be managed as aggressively as it is in any child with reflux, and a successful and safe reduction of symptoms can be expected with intensive management.