A growth factor-based strategy recently has been shown to induce the intrinsic repair of partial-thickness articular cartilage lesions, thereby obviating the need for transplanting cells or tissue. It was the purpose of the current study to ascertain whether this principle could be applied to full-thickness articular cartilage defects created in adult rabbits and mature miniature pigs. The transforming growth factor-beta1 contained within the authors' chondrogenic matrix-complex proved to be potent in its osteogenic capacity when liberated into the bone compartment of such lesions, inducing the rapid upgrowth of osseous tissue and vascular buds into the cartilage compartment. This is an unwanted response that must be prevented. A cell and blood vessel-excluding membrane (Millipore in rabbits and Goretex in miniature pigs) was inserted at the interface between cartilage and bone compartments, both of which were filled at the appropriate juncture with the chondrogenic matrix-complex. These structural barriers were effective in obstructing the up-growth of blood vessels into the cartilage compartment and in preventing the osteogenic tissue differentiation attributable to the presence of a vasculature.