The nucleus of the intervertebral disc in humans shows the most dramatic changes with age of any cartilaginous tissue. It originates from the notochord. In the foetus and infant, the nucleus contains actively dividing and biosynthetically active notochordal cells. The proteoglycans and other matrix components produced have a high osmotic pressure, imbibe water and maintain a hydrated structure which, though it has little mechanical strength, has a high swelling pressure which maintains disc turgor. In some species, the notochordal cells and the mucoid nucleus pulposus persist throughout adult life. However by about 4 yr of age in humans, the notochordal cells have disappeared to be replaced by those of chondrocytic appearance but of unknown origin. These cells continue to produce proteoglycans but also synthesize significant amounts of collagen. The nucleus becomes firmer and less hydrated and loses its transparent appearance. The cell density of the adult nucleus is very low with cells occupying less than 0.5% of tissue volume; each cell thus has to turn over and maintain a large domain of extracellular matrix. The density of living cells decreases with age, possibly because of problems with nutrient supply to this large avascular tissue. Proteoglycan concentration also falls, and nucleus hydration decreases markedly, the disc discolours and in many cases clefts and fissures form. In most adults, the disc nucleus degenerates eventually to a stage where it can no longer fulfil its mechanical role.