In general, there is no perfect method for esophageal replacement under consideration of the numerous associated risks and complications. The aim of this study was to examine a new material--small intestinal submucosa (SIS)--in alloplastic esophageal replacement. We implanted tubular SIS prosthesis about 4 cm in length in the cervical esophagus of 14 piglets (weight 9-13 kg). For the first 10 days, the animals were fed parenterally, supplemented by free given water, followed by an oral feeding phase. Four weeks after surgery, the animals were sacrificed. Only 1 of the 14 animals survived the study period of 4 weeks. The other piglets had to be sacrificed prematurely because of severe esophageal stenosis. On postmortem exploration, the prosthesis could not be found either macroscopically or histologically. Sutures between the prosthesis and the cervical muscles did not improve the results. Until now, the use of alloplastic materials in esophageal replacement has failed irrespective of the kind of material. As well as in our experiments, severe stenosis had been reported in several animal studies. The reasons for this unacceptable high rate of stenosis after alloplastic esophageal replacement seem to be multifactorial. Possible solutions could be transanastomotic splints, less inert materials, the decrease of anastomotic tension by stay sutures, the use of adult stem cells, and tissue engineering.