Martian regolith (unconsolidated surface material) is a potential medium for plant growth in bioregenerative life support systems during manned missions on Mars. However, hydrated magnesium sulfate mineral levels in the regolith of Mars can reach as high as 10 wt%, and would be expected to be highly inhibitory to plant growth.Disabling ion transporters AtMRS2-10 and AtSULTR1;2, which are plasma membrane localized in peripheral root cells, is not an effective way to confer tolerance to magnesium sulfate soils. Arabidopsis mrs2-10 and sel1-10 knockout lines do not mitigate the growth inhibiting impacts of high MgSO(4).7H(2)O concentrations observed with wildtype plants. A global approach was used to identify novel genes with potential to enhance tolerance to high MgSO(4).7H(2)O (magnesium sulfate) stress. The early Arabidopsis root transcriptome response to elevated concentrations of magnesium sulfate was characterized in Col-0, and also between Col-0 and the mutant line cax1-1, which was confirmed to be relatively tolerant of high levels of MgSO(4).7H(2)O in soil solution. Differentially expressed genes in Col-0 treated for 45 min. encode enzymes primarily involved in hormone metabolism, transcription factors, calcium-binding proteins, kinases, cell wall related proteins and membrane-based transporters. Over 200 genes encoding transporters were differentially expressed in Col-0 up to 180 min. of exposure, and one of the first down-regulated genes was CAX1. The importance of this early response in wildtype Arabidopsis is exemplified in the fact that only four transcripts were differentially expressed between Col-0 and cax1-1 at 180 min. after initiation of treatment.The results provide a solid basis for the understanding of the metabolic response of plants to elevated magnesium sulfate soils; it is the first transcriptome analysis of plants in this environment. The results foster the development of Mars soil-compatible plants by showing that cax1 mutants exhibit partial tolerance to magnesium sulfate, and by elucidating a small subset (500 vs. >10,000) of candidate genes for mutation or metabolic engineering that will enhance tolerance to magnesium sulfate soils.