Developing osteoarthritis, surgically induced in the right hind knee joint of guinea pigs by different procedures (A or B), was studied in animals maintained on either minimal or supplemented levels of dietary vitamin C. Procedure A, consisting of transecting the anterior cruciate and major portion of the medial collateral ligaments, resulted in a slower developing and less severe form of the disease than procedure B which also included a partial menisectomy. Regardless of the surgical procedure used, animals on minimal levels of ascorbate always exhibited more severe pathology than those on high levels. When compared with controls, a significant enhancement of acid phosphatase characterized arthritic cartilage in both supplemented and minimal diet groups, although the increase was 2-fold greater in the latter. In addition, a significant elevation of arylsulfatase A and B activities was observed only in the minimal diet group. Early stages of pathology in both diet groups were characterized by formation of repair cartilage which stained strongly with Safranin O on histologic sections. As the disease progressed, pitting, ulcerations, and eburnation occurred in the minimal diet group. Cartilage weight in normal joints was greater for guinea pigs kept on high levels of vitamin C. It is likely that this stimulated synthesis of cartilage in the supplemented animals protected against the erosion of the articular cartilage which characterized the more severe disease process in the guinea pigs on minimal levels of ascorbate.