The mechanisms for the differential response of articular cartilage to mechanical stimuli such as shear stress or hydrostatic pressure remain nuclear. Nitric oxide is implicated as an important mediator in chondrocytes exposed to shear stress. However, the effect of intermittent hydrostatic pressure on the release of nitric oxide from chondrocytes remains unclear. This study investi-gated the responses of osteoarthritic chondrocytes to mechanical stresses by analysis of matrix macromolecule gene expression and nitric oxide levels. Application of shear stress up-regulated nitric oxide release from osteoarthritic chondrocytes. The in creased nitric oxide release was associated with down-reg-ulation of matrix macromolecule gene expression. In contrast to shear stress, intermittent hydrostatic pressure did not increase nitric oxide release but was associated with up-regulaton of matrix macromolecule gene expression. The data presented here demonstrated that shear stress stimulated while intermit-tent hydrostatic pressure did not increase the release of nitric oxide from chon-drocytes. These data suggest that intermittent hydrostatic pressure is beneficial to cartilage and that shear stress is in favor of degeneration as a result of differ-ent effects on the matrix macromolecular gene expression.