Measurements of uptake in vivo of 3H-proline into 3H-hydroxyproline demonstrate that cartilage surfaces in rabbit knees with surgically induced osteoarthrosis (up to 3 months after operation) incorporated 2 to 5 times more activity into collagen than cartilage of control knees. The high uptake indicates that collagen synthesis was stimulated severalfold. In the lateral compartment of the experimental knee, which did not develop lesions, the 3H-proline metabolism was also stimulated, but this reaction subsided after 3 months. In the medial compartment, where the focal lesions developed, the stimulation continued. The newly made collagen was predominantly Type II; no evidence was found for a significant production of Type I collagen, even in the focal lesion on the medial tibial plateau more than a year after surgery. By radiochemical labelling with 3H-glucosamine,, an increase in the ratio of 3H-galactosamine to 3H-glucosamine was detected in all cartilage surfaces at intervals of 2-5 weeks after surgery. The increase was associated with the transient synovitis before lesions appeared, but not later. The observations suggest that synovitis and mechanical stresses are both important in inducing osteoarthrotic lesions.