OBJECTIVES: Donor site morbidity, including pneumothorax, can be a considerable problem when harvesting cartilage grafts for laryngotracheal reconstruction (LTR). Tissue-engineered cartilage may offer a solution to this problem. This study investigated the feasibility of using Hyalograft C combined with autologous chondrocytes to tissue engineer cartilage grafts for LTR in rabbits. STUDY DESIGN: Animal study. METHODS: Eighteen New Zealand white rabbits underwent LTR: 12 rabbits received autologous tissue-engineered cartilage grafts and 6 animals, serving as a positive control group, native auricular cartilage. To determine any differences in response to the site of implantation and any potential immune response to the scaffold, a second piece of engineered neocartilage and a non-cell-loaded scaffold were inserted paralaryngeally into a subset of the rabbits. The rabbits were sacrificed 3, 6, 8, 10, and 12 weeks after the LTR and their larynx examined. RESULTS: None of the 18 rabbits showed signs of respiratory distress. A smooth, noninflammatory scar was visible intraluminally. Histologically, the native auricular cartilage implants showed excellent integration without any signs of inflammation or cartilage degradation. In contrast, all tissue-engineered grafts and empty scaffolds revealed marked signs of an unspecific foreign body reaction, leading to a complete degradation of the neocartilage, whether implanted para- or intralaryngeally. CONCLUSION: In contrast to the success with which Hyalograft C has been applied in articular defect repair, our results indicate that, in rabbits, Hyalograft C initiates a foreign body reaction if implanted intra- or paralaryngeally, leading to cartilage degradation and possible graft failure. These findings suggest limitations on the environment in which Hyalograft C can be applied.