Problem Tissue engineering of human nasal septal cartilage represents an alternative technique for creating large quantities of autologous material for use in reconstructive surgery of the head and neck. Septal neocartilage constructs developed in vitro by the alginate method have demonstrated cartilaginous extracellular matrix production, but their biocompatibility and development in vivo remains largely unknown. Methods A murine model was used to examine the behavior of neocartilage constructs in vivo. Chondrocytes collected from donors undergoing septoplasty were expanded in monolayer and suspended in alginate beads for three-dimensional culture in media containing human serum and growth factors. After in vitro incubation for 5 weeks, the neocartilage constructs were implanted subcutaneously in the dorsum of athymic mice for 30 days (n=3). The mice were sacrificed and the constructs were explanted for assessment of cell viability, gross morphology, and histology. Results The mice survived and tolerated the implant well. Infection and extrusion were not observed. Neocartilage constructs maintained their general shape and size, and demonstrated cell viability after implantation. Explanted constructs were firm and opaque, sharing closer semblance to native septal tissue relative to the gelatinous, translucent pre-implant constructs. On hematoxylin and eosin staining, the explanted constructs exhibited distinct morphologies characteristic of native tissue, which were not observed in pre-implant constructs. Conclusion Neocartilage constructs are viable in an in vivo murine model. The morphologic and histologic features of explanted constructs more closely resemble native septal tissue when compared to pre-implant constructs. Significance Septal neocartilage constructs are biocompatible and demonstrate potential for in vivo maturation with eventual clinical application.