This is a histological and autoradiographic study of certain factors responsible for degeneration occurring in immobilized normal rat knees. Knees which have been denervated, immobilized and denervated, and immobilized with and without weight-bearing were studied. The weight-bearing and non-weight-bearing immobilized knees underwent nearly identical progressive degenerative change. The denervated immobilized knees showed similar but less extensive degeneration. The knees which were only denervated showed few changes. On the basis of our study, and studies by previous authors, we have come to the following conclusions applicable to the rat knee:

1. Up to ninety days of immobilization, adhesions play a minor role in the observed cartilage degeneration.

2. Up to ninety days, peripheral, unapposed cartilage is affected relatively little by immobilization.

3. Up to ninety days, weight-bearing and normal joint motion are not necessary to maintain adequate nutrition to large portions of articular cartilage.

4. Absolute, rigid immobilization as opposed to nearly complete immobilization does not prevent or increase the degenerative change known to occur with immobilization.

5. The pressure of weight-bearing is not a major determinant of cartilage degeneration in the immobilized joint.

6. Static compression present between small areas of constantly apposed articular cartilage is a major determinant leading to chondrocyte death and cartilage degeneration.

7. Pressures resulting from abnormal, forced positions are not necessary to produce cartilage degeneration in immobilized joints.

8. Sulphate deposition is not grossly altered in the epiphyseal and articular cartilage up to ninety days following denervation of muscles serving the knee.

9. Although there are slight similarities between the degeneration resulting from immobilization of the rat knee and human osteo-arthritis, these processes are not analogous.