Beta-endorphin and substance P were immunolocalized in the articular cartilage, synovial membrane and fibrous joint capsule of dogs. Twelve adult greyhounds were randomly assigned to one of three groups: control, limited exercise, or regimented exercise. On day 0, biopsies of articular cartilage and joint capsule were obtained from the left shoulder joints of dogs receiving limited and regimented exercise. On day 72, biopsies of joint capsule from right and left shoulders and articular cartilage from the right shoulder joint were analysed for the presence of glycosaminoglycans (GAG) and for immunolocalization of substance P and beta-endorphin. Regimented exercise increased the presence of GAGs and immunolocalization of substance P and beta-endorphin in articular cartilage and synovial membrane compared to day 0 biopsies and untreated controls. Localization of beta-endorphin became prominent in and around the chondrocytes. Substance P was increased in chondrocytes and extracellular matrix. Concomitant changes in localization of beta-endorphin and substance P may have a role in the modulation of the microphysiological environment, metabolism, or function of joint tissues in response to low-impact exercise.