Resistance to oral feedings occurring during the course of chronic gastroesophageal reflux (GER) in infants has received little attention in the literature. Accordingly, we reviewed the clinical courses of 600 infants of < 24 months of age with GER seen over an 8-year period to determine the prevalence and course of this problem. After excluding infants with severe neurologic disease, craniofacial disorders, or a history of esophageal surgery, 25 infants were found to have resistance to oral feedings that was severe enough to warrant tube feedings for nutritional support. Sixteen of these 25 infants had a history of resistance to oral feeding antedating a diagnosis of GER, whereas nine developed resistance to feeding during the course of therapy. Gestational age, age at onset of GER symptoms, severity of GER, presence/severity of esophagitis, type of medical therapy, need for fundoplication, or postfundoplication complications were similar in these two groups. When the clinical records of these 25 infants were compared to an age- and sex-matched infant population with GER but without feeding resistance, no differences were noted in severity of GER or the presence/severity of esophagitis. However, failure to thrive and the need for fundoplication were significantly more common in the feeding resistance group (p < 0.001). Among those infants with neurodevelopmental evaluation, mild delay was seen more commonly in the infants with feeding resistance but fell short of statistical significance (p = 0.08). Our observations suggest that resistance to oral feedings is an uncommon but severe problem associated with GER in infancy.(ABSTRACT TRUNCATED AT 250 WORDS)