Although the role of growth factors in the regulation of phenotype, maintenance, and repair of cartilaginous tissues has been extensively evaluated, the response of intervertebral disc to growth factors has not been investigated. A tissue culture system for annular, transitional, and nuclear regions of mature canine intervertebral disc was devised to assess the proliferative response, as determined by 3H-thymidine incorporation, and the biosynthetic response, assayed by 35S-sulfate incorporation into proteoglycan, of these tissues to growth factors. The culture system achieved steady-state conditions in serum-free mediums at 4 days and was perturbed by plasma-derived equine serum, fetal calf serum, insulin-like growth factor-1, epidermal growth factor, fibroblast growth factor, and transforming growth factor-beta. Incorporation rates by the tissue regions of up to five times the control rate were recorded; the nucleus and transition zone responded more than anulus. Transforming growth factor-beta and epidermal growth factor elicited greater responses than fibroblast growth factor; insulin-like growth factor-1 produced a marginally significant response in the nucleus and no response in the anulus and transition. The intervertebral disc appeared to respond to the growth factors differently than cartilage, and this may represent inherent differences in cell biology. The biologic significance and basis of these responses require further evaluation. However, the responses observed, particularly in the nucleus and transition zone suggest the possibility that disc repair can be modulated by growth factors. A therapeutic approach to degenerative disc disease involving enhanced tissue repair by exogenous growth factors would be of great clinical significance.