Fragments of calf articular cartilage maintained in organ culture were subjected to continuous mechanical pressure applied by means of lead weights of differing sizes. Increasing the pressure from approximately 7.5-30 kgfcm-2 proportionately decreased the breakdown of proteoglycans as measured by the release of [35S]sulphate from prelabeled cartilage. The difference was observed as early as 24 hours after culture. During the first 24 hours after removal of a 30 kgfcm-2 pressure the release of [35S]sulphate was slightly greater than that of the nonweight-bearing controls and then subsequently returned to the level of the controls. Application of a mechanical pressure of 30 kgfcm-2 to calf articular cartilage reduced the incorporation of [35S]sulphate to about half the level of the nonweight-bearing controls. A pressure of 15 kgfcm-2 had no significant effect upon [35S]sulphate incorporation. The production of lactate by the cartilage under the influence of 30 kgfcm-2 for 4 days was not significantly different from that of nonweight-bearing controls indicating the retained viability of the tissue. The present study indicates that proteoglycan metabolism of calf articular cartilage in vitro is capable of responding rapidly to variations in applied load. The potential importance of this finding in terms of the functional demands of articular cartilage is apparent, and it can be speculated that a failure of this adaptability of the chondrocytes is an important factor in the etiology of degenerative joint disease.