Arabidopsis thaliana was evaluated for its response to the spaceflight environment in three replicated experiments on the International Space Station. Two approaches were used; GFP reporter genes were used to collect gene expression data in real time within unique GFP imaging hardware, and plants were harvested on orbit to RNAlater for subsequent analyses of gene expression with using Affymetrix and SAGE transcriptome analyses. Three tissue types were examined (leaves, hypocotyls and roots) and compared to analyses conducted with whole plants. Transcriptome analyses with whole plants suggested that the spaceflight environment had little impact on the transcriptome of Arabidopsis, however, closer examination of selected tissues revealed that there are a number of tissue-specific responses that Arabidopsis employs to respond to this novel environment.