The effects of compressive stress on the rate of proteoglycan synthesis and release were determined in bovine articular cartilage from 4–5-month-old animals. Full depth cartilage explants were compressed in an unconfined configuration at various stresses ranging up to 1.0 MPa. At mechanical equilibrium (after 24 h), no significant changes were detected in the rate of [35S]-sulfate (³⁵SO₄) incorporation at the low level of compressive stresses used (less than 0.057 MPa). At an intermediate level of compressive stress (0.057, 0.1, 0.5 MPa), ³⁵SO₄ incorporation rates were reduced to ∼60% of control values. At the highest level compressive stress (1.0 MPa) studied, ³⁵SO₄ incorporation rates were further reduced to ∼20% that of controls. Recovery experiments at intermediate stress levels showed increased rates of ³⁵SO₄ incorporation at 24 h after compression. In explants loaded for 24 h at stresses of 0.1 MPa or higher, there was a stress-dose dependent inhibition of proteoglycan release into the media (up to 61% at 1.0 MPa), and proteoglycan release rates did not return to control values following a 24 h recovery period. While cartilage composition and biosynthetic activity were found to vary significantly with depth in control cartilage, the observed suppression (% change) in biosynthetic activity was relatively uniform with depth in both loading and recovery experiments. The study indicates that compression of the tissue to physiological strain magnitudes serves as a signal to modulate chondrocyte biosynthetic and catabolic responses through the depth of cartilage, while prolonged compression at higher strains may be responsible for tissue and cell damage.