<jats:title>Abstract</jats:title><jats:sec><jats:title>Objective</jats:title><jats:p>Although cartilage lesions occur in the ankles, osteoarthritis rarely develops in the ankles, suggesting that ankle cartilage can up‐regulate mechanisms to repair the damaged matrix. To define these processes, we compared cartilage samples obtained from normal tali and from lesional sites of damaged tali.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Cartilage samples were obtained from the tali of normal ankles and from 3 sites on tali with lesions (the lesion, adjacent to the lesion, and far removed from the lesion). Cartilage was analyzed for type II collagen (CII) messenger RNA, C‐terminal type II procollagen propeptide (CPII), the collagenase cleavage neoepitope (Col2‐3/4C<jats:sub>short</jats:sub>), and the denaturation epitope (Col2‐3/4m). For the assessment of type IX collagen, the COL2 and NC4 domains were evaluated. The cartilage samples were also assayed for glycosaminoglycans, epitope 846 of aggrecan, and DNA.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The DNA content, epitope 846, COL2(IX), and the denaturation epitope were significantly increased in lesional cartilage. Although there was a tendency toward an increase in CII content and CPII, the increase did not reach significance. Neither the NC4(IX) domain nor Col2‐3/4C was elevated. Surprisingly, changes in cartilage both adjacent to and remote from the lesion were similar to those in the lesion.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>The changes observed in cartilage obtained from the lesion and from sites adjacent to the lesion were not surprising; however, the changes in cartilage obtained from sites remote from the lesion were unexpected. This up‐regulation of matrix turnover in ankles with degenerative lesions may indicate a physiologic response of the entire articular surface to repair the damaged matrix, which is not restricted to the lesion site. This suggests that there may be some mechanism of communication across the cartilage. The response by ankle cartilage obtained from a site remote from the lesion has not been observed in the knee.</jats:p></jats:sec>