The clinical and radiographic findings of eight low-birth-weight neonates (mean, 900 g) with perforations of the duodenum or jejunum associated with transpyloric feedings are reported. In four patients, the perforations occurred distal to any known tube position. In experimental studies in young rabbits, Silastic or polyvinyl chloride tubes were sewn in place with the tube tips in the proximal duodenum or proximal jejunum, and either normal oral feedings or feedings through the tubes were given. Perforations and gross or microscopic abnormalities of the bowel mucosa in the area of the tubes and beyond were more frequent in rabbits with tube feedings than those given normal oral feedings. It appears that tube feedings induce some degree of mucosal damage and contribute to bowel perforation.