We report on the deformation behavior of single silica microspheres. For the first time a detailed discussion on the quantitative evaluation of force-deformation data in the elastic and plastic regime is given. The microspheres are compressed between two flat plates of a custom built manipulation device supported by a scanning electron microscope. The device allows a high sample throughput enabling full statistical evaluation of force-deformation data of single microspheres. Existing theories describing the deformation behavior of single spheres are discussed and applied to the elastic and plastic deformation regime of silica microspheres. The results obtained from the theories are compared between each other and values reported in literature. The silica microspheres exhibit a significantly different deformation behavior than expected from bulk fused silica, i.e. a distinct plastic deformation behavior. Furthermore, a significant decrease in Young's modulus and hardness was observed caused by high porosity and reduced crosslinking of silicon atoms, respectively, that is inherent to silica produced by Stober synthesis. However, the calculated contact pressures exceed the compressive strength of bulk fused silica by at least a factor of two as an effect of a reduced amount of material flaws in microstructures. (c) 2013 The Society of Powder Technology Japan. Published by Elsevier B.V. and The Society of Powder Technology Japan. All rights reserved.