Human intervertebral discs were used to develop an intact whole disc organ culture system with long-term cell viability. To develop and validate a long-term organ culture system for intact human intervertebral discs, in which the potential for biologic repair of disc degeneration can be studied. Intervertebral disc degeneration is a common cause of back pain, which can be costly to the health care system and have a negative impact on the quality of life of the patient. Once injured the adult human intervertebral disc seems incapable of intrinsic repair, but the early stages of disc degeneration can potentially be retarded or even reversed by the administration of growth factors to promote new extracellular matrix synthesis. Intervertebral discs were prepared by three isolation techniques and placed in free swelling organ culture. Cell viability, disc swelling, glycosaminoglycan content, and extracellular matrix degradation were assessed under a variety of culture conditions. Human intervertebral discs isolated with intact cartilage end plates retained cell viability and did not undergo matrix degradation when cultured for 4 weeks with both a high and low nutrient level. This contrasted with the excessive cell death that was observed if the cartilage end plates were removed before culture or if vertebral bone was retained. Retention of the cartilage end plates limits tissue swelling and permits efficient nutrient supply, thus allowing viable long-term organ culture. The availability of such a system will permit the repair potential of therapeutic candidates to be studied in human discs with naturally occurring degeneration. Furthermore, the system is simple and economical, as no apparatus is needed to limit the detrimental effects of excessive tissue swelling.