Spontaneous synovitis has been detected in the stifle joints of control Wistar rats in 4-wk and 2-yr toxicity studies, and a specific site was found to be predisposed to synovitis. The incidence of synovitis was 27.5% for males in the 4-wk study and 40.0% for males and 16.0% for females in the 2-yr study. The severity was not increased with aging. The degenerative changes, including chondroid metaplasia of the cruciate ligaments of the stifle and/or the surrounding connective tissue at the border of the cruciate ligaments of the stifle, were present even in younger animals, and moreover there was a good correlation between synovitis and chondroid metaplasia of the cruciate ligaments of the stifle and the surrounding connective tissue at the border of the cruciate ligaments of the stifle. Vascular changes, including the development of fibrin-containing thrombi, were observed in the surrounding connective tissue at the border of the cruciate ligaments of the stifle. It is speculated that the pathogenesis of the observed synovitis reflects joint instability that induces mechanical damage of the synovium.