Children with a variety of genetic, metabolic, and neurologic disorders can suffer from severe feeding intolerance that is unresponsive to medical, surgical, and nutritional therapy. Developmentally disabled tube-fed children with severe upper gastrointestinal symptoms that persisted after fundoplication who were unresponsive to all medical, surgical, and nutritional interventions underwent a thorough gastrointestinal evaluation, including gastroscopy, pH-metry, upper gastrointestinal barium series, and gastric emptying studies. They were placed on a low-fat diet, and the symptoms before and after the diet were compared. The patients were then rechallenged with incremental increases in fat until the symptoms recurred or the patients reached their former fat concentration. Six children meeting the study criteria were evaluated. Four of these patients had a significant improvement in symptoms, oral intake and feeding tolerance with a decrease in fat intake, and relapse of symptoms when fat calories were increased. Improvement occurred in children who had been intolerant to duodenal feeding. We were subsequently able to wean two children from tube feeding. Dietary fat can provoke upper gastrointestinal symptoms in children with gastric and intestinal dysmotility. Short-term manipulation of dietary fat intake can improve tolerance to feeding.