In March 2006 murine Bone Marrow Stromal Cells (BMSC) were flown in the Soyuz 12S to the International Space Station to investigate the effects of microgravity on their osteogenic potential in a three-dimensional environment. BMSC were grown in porous bioceramic Skelite disks (dia 9 mm x T 1.2 mm). The constructs were exposed to microgravity for ca. 8 days then fixed for RNA extraction. While the flight experiment was performed in fully automated hardware inside the KUBIK incubator one group of control samples were incubated inside manually operated hardwares (flight control) and the other control group was incubated under routine laboratory conditions (lab control). The altered gene expression profile was analyzed by Mouse Gene 1.0 ST array (Affymetrix) representing whole-transcript coverage. Each one of the 28853 genes is represented on the array by approximately 26 probes spread across the full length of the gene providing a more complete and more accurate picture of gene expression than the 3 based expression array design. A few days of microgravity were sufficient to determinate at least at the molecular level an effect in the BMSC; this response expressed a stress condition able to determinate consequences on several compartments and cellular functions. In particular it seems to promote a gene expression known to be associated with neurogenic activity (e.g. axon guidance) perhaps promoting the BMSC capability to be committed in that direction. The osteo-induction by dexamethasone-based medium due to the short duration of stimulation did not have the possibility to manifest itself at the phenotypic level but only partially at the molecular level.