The functions of caveolae, the characteristic plasma membrane invaginations, remain debated. Their abundance in cells experiencing mechanical stress led us to investigate their role in membrane-mediated mechanical response. Acute mechanical stress induced by osmotic swelling or by uniaxial stretching results in a rapid disappearance of caveolae, in a reduced caveolin/Cavin1 interaction, and in an increase of free caveolins at the plasma membrane. Tether-pulling force measurements in cells and in plasma membrane spheres demonstrate that caveola flattening and disassembly is the primary actin-and ATP-independent cell response that buffers mem-brane tension surges during mechanical stress. Conversely, stress release leads to complete caveola reassembly in an actin-and ATP-dependent process. The absence of a functional caveola reservoir in myo-tubes from muscular dystrophic patients enhanced membrane fragility under mechanical stress. Our findings support a new role for caveolae as a physio-logical membrane reservoir that quickly accommo-dates sudden and acute mechanical stresses. INTRODUCTION