The knee joints from males of two strains (CBA/ORT and STR/ORT) were studied histologically. The incidence of degenerative joint disease was very high in the STR/ORT strain. Degeneration of the cartilage invariably occurred first at the interface of the cruciate ligament and articular cartilage of the tibia. Lesions were only seen on the medial tibial and later the medial femoral condyles. Blocks of fibrillated, uncalcified cartilage were gradually lost across the condyle, leaving the tidemark as a secondary articulating surface. Meanwhile the subchondral bone thickened and erosion continued through the calcified cartilage into the underlying bone. A statistically significant relationship was found between the development of the lesion and (a) medial dislocation of the patella, (b) calcification and ossification of the medial collateral ligament. Patella dislocation gave rise to extensive cartilaginous and bony metaplasia of the synovial tissue. In joints with advanced degeneration there was often evidence of a slight lateral subluxation of the femur relative to the tibia.