The relationship existing between cell morphology and cell metabolism, and the role of mechanical load in bone remodelling are well-known. In osteoblasts, PGE₂ mediates part of the response to mechanical stress and induce cell shape changes. We studied the influence of gravity variations on osteoblast morphology and its relationship with PGE₂ synthesis during a parabolic flight. ROS 17/2.8 osteosarcoma cells flew 15 or 30 parabolae. We measured cell area and shape factor after fluorescein staining with a semi-automatic image analyser and PGE₂ levels by RIA. Significant flight-induced shape changes consisted in a decrease in cell area and an increase in shape factor (cell irregularity), in some cells, as compared to ground controls. This heterogeneity in cell response might be explained by a cell-cycle sensitivity to mechanical stress. A 45 min pretreatment with indomethacin inhibited the flight-induced increase in cell irregularity whereas cell area remained decreased. PGE₂ levels were higher in flight than in ground controls. Linear regression analysis showed a significant negative relationship between cell area and PGE₂ synthesis. We concluded that ROS 17/2.8 are highly sensitive to gravitational variations and that PGE₂ is partly implicated in cell shape changes observed during parabolic flight. However, other mechanisms than PGE₂ synthesis condition ROS 17/2.8 morphology in response to mechanical changes.