The influences of the strenuous running training program on the knee joint articular cartilage was studied in six female beagle dogs. At the age of 15 weeks, the dogs started running on a treadmill inclined 15 degrees uphill. Thereafter, the dogs were trained for 40 weeks, five times a week. For the final 15 weeks, the dogs ran 20 km/day. Six age-matched female beagles served as controls. The cartilage surfaces were intact after the running exercise. The training reduced the thickness of the uncalcified cartilage by 6% in the medial femoral condyle. The glycosaminoglycan concentration was reduced an average of 11% on the summits of the femoral condyles. The reduction was most pronounced (41%) in the superficial 50-micron cartilage zone. In other regions of the knee, such a decrease of glycosaminoglycans was not observed. A shift to strenuous running voided the increase in cartilage thickness and proteoglycan content previously observed after moderate running. Strenuous running induced marked depletion of proteoglycans from the superficial layer of the femoral condyles at sites subjected to highest impact loads.