The effect of overuse and overuse combined with axial peak overloading on the knee joints of living rabbits has been investigated. A specially constructed apparatus was used for this purpose. Physical and biochemical changes are reported and include: 1. Early and progressive damage to the articular cartilage surface shown by the scanning electron microscope. 2. The presence of an increased amount of prostaglandin E in the synovial fluid. 3. A reduction of cyclic 3'--5' monophosphate in the subchondral bone. 4. Late changes which were consistent with osteoarthritis. These changes were found only in the joints subjected to simultaneous overuse and peak overloading. The results suggest that: 1. Cartilage damage and chemical changes in the subchondral bone are simultaneous and are both responsible for eventual degenerative changes. 2. Frictional overuse alone does not seem to be responsible for the production of oesteoarthritis.