A new mechanical explant test system was used to study the metabolic response (via proteoglycan biosynthesis) of mature, weight-bearing canine articular cartilage subjected to static and dynamic compressive stresses. Stresses ranging from 0.5 to 24 MPa were applied sinusoidally at 1 Hz for intervals of 2-24 h. The explants were loaded in unconfined compression and compared to age-matched unloaded explants. Both static and dynamic compressive stress significantly decreased proteoglycan biosynthesis (range 25-85%) for all loading time intervals. The inhibition was proportional to the applied stress but was independent of loading time. After rehydration upon load removal, the measured water content of the loaded explants was not different from the unloaded explants for all test variables. Autoradiographic and electron microscopic analysis of loaded explants showed viable chondrocytes throughout the matrix. Our results suggest that the decreased metabolic response of cyclically loaded explants may be dominated by the static component (RMS) of the dynamic load. Furthermore, the observed decreased metabolism may be more representative of the in situ tissue response than that of unloaded explants, in which we found an increasing rate of metabolism for up to 6 days after explant removal.