The influence of static and intermittent stress on articular cartilage metabolism was examined in vitro. Full-thickness plugs of cartilage from femoral condyles of normal adult dogs were cultured while static or cyclic stresses were applied for 2 hours. The plugs were then incubated under atmospheric pressure for 2 hours in medium containing radioactive label, to provide measurements of net synthesis of glycosaminoglycan (GAG) or protein. As a control, cartilage from the same knee was cultured in the apparatus at atmospheric pressure. When cartilage plugs were exposed to static stress, or to cyclic stresses at a duty cycle of 60 seconds on/60 seconds off, net GAG synthesis was suppressed to 30—60% of that in controls. In contrast, when a duty cycle of 4 seconds on/11 seconds off was used, GAG synthesis was increased by 34%. The duty cycle which increased GAG synthesis did not affect protein synthesis or tissue contents of DNA, uronic acid, or water. At the cycle which suppressed GAG synthesis, protein synthesis and uronic acid content were decreased, and water content was increased. As judged by uptake of ¹⁴C-aminoisobutyric acid and ¹⁴C-xylose, the above changes in GAG synthesis do not appear to have been due to changes in diffusion of nutrient molecules through the cartilage during loading.