For thirty-two areas of cartilage from nine osteo-arthritic and four "normal" femoral heads a histologic-histochemical grade was assigned as an index of severity of the osteo-arthritic process. The DNA and hexosamine concentrations were determined as indicators of cell density and polysaccharide content, respectively, and the incorporation rates of ³H-thymidine and ³⁵SO₄ were measured as indicators of synthesis of DNA and polysaccharide, respectively. From these data and the correlation analyses of them, the following information was derived:

1. Osteo-arthritis is a focal disease and there is considerable variation in the severity of the lesion on each osteo-arthritic femoral head.

2. There is excellent direct correlation between the severity of the process and the rates of DNA and polysaccharide synthesis. At a specific histologic-histochemical degree of "severity," however, the reparative mechanisms seem to "fail," and to decrease with advancing disease.

3. There is a significant inverse correlation between the severity of the process and the polysaccharide concentration, but there is no correlation between the cell density (as reflected by DNA levels) and the severity of the disease.

4. The cartilage covering osteophytes is less severely involved histologically and shows less diminution in the concentrations of polysaccharide. The synthesis of polysaccharide at these sites is increased as compared with that in non-osteophytic arthritic tissue.

On the basis of these data, a scheme for the biochemical and metabolic response of cartilage to the chronic stress of osteo-arthritis is advanced.