Articular cartilage from the knees of 4 dogs whose ipsilateral paws had been transected 6 weeks earlier (knee,,,,,), and from their contralateral knees (knee,,), was examined. Knee,,,,, did not bear weight as a result of the surgical procedure but active motion of the joint, determined with an angular displacement monitor during walking, was comparable to that of knee,,.. In comparison to knee,, cartilage, knee,,,, samples showed decreases in thickness, Safranin-0 staining of the matrix, and uronic acid content (mean, 24.4%), and increase in water content (mean, 5.9%). Incorporation of into proteoglycans was 34-67% less in knee,,,,, than in knee,,, cartilage. Proteoglycan (PC) aggregation in knee,, cartilage was normal, whereas in knee,,... cartilage the bulk of the proteoglycans, and also those that had been newly synthesized ('5S-proteoglycans), did not exist in aggregates. This defect in aggregation was due, at least in part, to an abnormality in the hyaluronatebinding region of the core protein of the proteoglycans, since they did not interact in vitro with hyaluronic acid These changes are essentially identical to those shown