We have examined the morphological changes in chondrocytes after exposure to experimental hypergravity. Tibial epiphyseal cartilages of 17-days-old mouse fetuses were exposed to centrifugation at 3G for 16 h mimicking hypergravitational environment (experimental group), or subjected to stationary cultures (control group). Centrifugation did not affect the sizes of epiphyseal cartilage, chondrocyte proliferation, type X collagen-positive hypertrophic zone, and the mRNA expressions of parathyroid hormone-related peptide and fibroblast growth factor receptor III. However, centrifuged chondrocytes showed abnormal morphology and aberrant spatial arrangements, resulting in disrupted chondrocytic columns. Through histochemical assessments, actin filaments were shown to distribute evenly along cell membranes of control proliferative chondrocytes, while chondrocytes subjected to centrifugal force developed a thicker layer of actin filaments. Transmission electron microscopic observations revealed spotty electron-dense materials underlying control chondrocytes' cell membranes, while experimental chondrocytes showed their thick layer. In the intracolumnar regions of the control cartilage, longitudinal electron-dense fibrils were associated with short cytoplasmic processes of normal chondrocytes, indicating assumed cell-tomatrix interactions. These extracellular fibrils were disrupted in the centrifuged samples. Summarizing, altered actin filaments associated with cell membranes, irregular cell shape and disappearance of intracolumnar extracellular fibrils suggest that hypergravity disturbs cell-to-matrix interactions in our cartilage model.The unique mechanical properties of the cartilage are conferred by its avascular composition and the complexity of its extracellular matrices including collagen fibrils, aggrecan, link proteins and so forth. Mesenchymal condensation, chondrocytic differentiation and subsequent matrix synthesis are genetically programmed, and regulated by microenvironmental influences such as soluble mediators, e.g., parathyroid hormone-related peptide (PTHrP) and fibroblast growth factor receptor III (FGFR3) (1, 2, 14). Currently, however, many investigators are paying attention to the fundamental role played by mechanical loading in chondrocyte regulation and cartilage dysfunction. Gravity, the force of attraction between all masses in the universe, can be understood as a source of loading upon chondrocytes and their surroundings. Altered gravity has been shown to affect