The articular cartilage from nineteen osteoarthritic and fourteen normal control adult human knee joints was analyzed for changes in water content, proteoglycan composition and structure, glycosaminoglycan synthesis rates, and cell content. We found no significant differences between visually intact cartilage from osteoarthritic knee joints and cartilage from control joints for any of the parameters studied. In osteoarthritic specimens in which the cartilage surface was not intact the biochemical changes depended on the degree of fibrillation. Surface-fibrillated specimens had a higher water content in the surface layers but no change in the content or synthesis rate of glycosaminoglycan. Deeply fibrillated cartilage, however, had an increased water content through its full depth, and there was a decrease in both the rate of synthesis and the content of glycosaminoglycans. Clinical Relevance: The results of this study suggest that degenerative changes in osteoarthritic knees are focal in origin and that corrective osteotomy or unicompartmental joint replacement might be rational procedures for knees in which the cartilage in all of one compartment is visually intact.