All tissues of the joint are affected in some way in osteoarthritis because the joint is an interactively functioning unit. Our goal was to investigate the combined responses of articular cartilage and subchondral bone to altered loading conditions to improve our understanding of the physiology of these two components and, ultimately, the pathophysiology of osteoarthritis. A group of 20 female beagle dogs were divided pairwise into runners (n = 10) and controls (n = 10). The running training on a treadmill started at the age of 15 weeks, and during the following 40 weeks the running distance was gradually increased to 40 km/day with a 15° uphill inclination. With this daily running distance the beagles ran another 15 weeks. The samples for histology were taken from 11 different locations of the knee joint. Subchondral bone and articular cartilage histomorphometry was carried out in three different regions of the specimens (central, middle, and peripheral regions) using an image-analyzing system and an eyepiece graticule. In all regions of the articular cartilage, both the uncalcified and calcified cartilage showed slightly increased thickness in the runner dogs. The change was more evident in the peripheral and the central areas. The thickness of the subchondral bone plate tended to be higher in runners, too. Bone histomorphometric parameters showed significant signs of increased remodeling. The most notable change was the enlargement of the bone formation surface. The most intense remodeling was usually observed either centrally or peripherally in the articular surface. The strongest increase in trabecular bone volume and thickness of the cartilage was recorded in the femoropatellar area. These topographically confined and separate responses of the articular cartilage and subchondral bone to long-distance running are presumably adaptive processes that provide better congruence and biomechanical stability to the articulating bone ends. Under pathologic conditions these processes may initiate the subchondral etiopathogenesis of osteoarthritis by impairing the shock-absorbing capacity of the joint.