We studied whether cyclic loading is harmful to degraded cartilage. Sets of four cartilage-bearing sesamoid bones were dissected from 5-year old cows. One bone from each set was cultured for 17 h in control medium to serve as an ex vivo control. The three others were cultured for 1 week in control medium to which 0, 10 or 300 ng/mL retinoic acid (RAc), which depletes the cartilage matrix of proteoglycans, had been added. Two were then cultured for another week in control medium. During the last week, one of the two was subjected to a cyclic load (1 MPa, 0.2 Hz). Following treatment with RAc, glycosaminoglycan content and synthesis were significantly decreased, as confirmed by safranin O staining and autoradiography. They were further diminished by loading during the second week of culture. Increased amounts of 3-B-3(-)epitope were found in cartilage that had been treated with 300 ng/mL RAc and then loaded. While loading cartilage matrix that was only slightly degraded proved to be damaging, loading severely degraded cartilage matrix apparently induced osteoarthritic-like changes.