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Osteoarticular defects present a reparative challenge to orthopaedic surgeons. Osteoarticular allografts provided a promising solution. Unfortunately, many of these allografts failed secondary to articular cartilage degeneration. To determine the role of the extracellular matrix in graft failure, the authors have characterized the proteoglycan content of cartilage from grafts that failed early (2-4 years) and grafts that failed late (approximately 8 years) and compared this with normal cartilage. Cartilage was removed from all specimens. Proteoglycans were extracted and characterized based on molecular size and reactivity with antibodies. Protein and proteoglycan contents of early and late failure grafts were significantly lower per gram of tissue than normal cartilage. Patterns of distribution of associated proteoglycans and dissociated proteoglycans differed between early and later failure grafts and both were different from normal cartilage. Early failure cartilage contained less keratan sulfate proteoglycan with a different distribution of molecular sizes. Chondroitin sulfate epitopes showed discordance between early failure and normal cartilage and concordance between normal and late failure cartilage. These data show distinct differences in proteoglycan content between failed graft and normal cartilage and also between cartilage from grafts that failed early and late. Proteoglycan content and glycosaminoglycan substitution were altered in all specimens. Maintenance of a more normal extracellular matrix will be required to preserve function in these grafts for longer periods.