The evolution of osteoarthritis (OA) was compared in male and female STR/ORT mice and in male CBA mice with particular emphasis on the changes in para-articular structures which occur before the classical degenerative phenomena in the articular cartilage of the knee. In male STR but not female STR mice or male CBA mice, chondro-osseous metaplasia was found in the tendinous structures which surround the joint and in the major ligamentous entheses such as the patellar ligament. This change was detectable from the age of three months. By contrast, changes in the articular surfaces of the knee were never detected before four months while the total patellar proteoglycan content in male STR animals increased from three months. Line density profile measurements on radiographs of the knees revealed that changes in the bone density of the sub-chondral zone of the articular surfaces only increased in affected animals after the development of severe OA changes in the joint. It is suggested that the model of OA which develops in male STR/ORT mice is secondary to soft tissue changes, particularly chondro-osseous metaplasia in para-articular structures.