Sulfur mustard [bis-(2-chloroethyl)-sulfide; SM] exposure leads to blister formation in skin of exposed individuals. This study examined SM-induced changes in gene expression using cDNA microarrays in skin from mice cutaneously exposed to SM. Ear skin from five mice, paired as SM-exposed right ear and vehicle control left ear at six dose levels (0.005, 0.01, 0.02, 0.04, 0.08, and 0.16 mg), was harvested at 24 h. Alterations in gene expression were analyzed using cDNA microarrays containing 1,176 genes. Genes were selected on the basis of all mice (N=5) in the same dose group demonstrating a ≥2-fold increase or decrease in gene expression in SM-exposed tissue compared to control skin at all six SM doses. When comparing skin exposed at all six SM doses with controls, a total of 19 genes within apoptosis, transcription factors, cell cycle, inflammation, and oncogenes and tumor suppressors categories were found to be up-regulated; no genes were down-regulated. A comparison of skin exposed to low (0.005 and 0.01 mg) and high (0.08 and 0.16 mg) doses of SM showed differences in the number and category of genes that were up- or down-regulated. Low level SM primarily altered transcription factors and repressors as well as genes involved in the cell cycle (e.g., cdc25B; cyclins) and apoptosis (e.g., GADD45; TNF receptor ligands); whereas high level SM also altered genes related to cytokines, chemokines, growth factors and hormones (IL-1β, MCP-1, MIP-1α,, and MIP-2). The results of this study provide a further understanding of the molecular responses to cutaneous SM exposure, and enable the identification of potential diagnostic markers and therapeutic targets for treating exposure to low and high levels of SM.