We employed cDNA microarrays to examine gene expression in cultured normal human epithelial cells (NHEK) exposed to the vesicating agents, sulfur mustard (2,2'-dichlorodiethyl sulfide, HD) and Lewisite (2 chlorovinyl-dichloroarsine, L). cDNA probes derived from cells exposed to HD at 100 μM for 0 (control) 4, 8 and 24 hours were used to hybridize human cytokine/receptor microarrays (Clontech cat. no. 7744-1). In other experiments gene expression was examined in NHEK cells exposed to lewisite at 1.0 μM for 0 (control) 4, 8 and 24 hours. Both HD and L rapidly induced the expression of IL-8 to high levels. Lewisite was also found to induce an IL-1 agonist and an IL-6 receptor component but expression of various growth factors was downregulated. HD modulated expression of many more inflammation-related genes than L which included upregulation of tumor necrosis factor, several growth factors and chemoattractants. HD treatment downregulated expression of at least 10 genes of which 7 were growth factor, or growth factor related. In a second set of experiments, SV40-immortalized keratinocytes (IHEK) and IHEKs stably transfected with an expression vector containing the interleukin 10 (IL-10) were exposed to c for periods of 4, 8 and 24 hours and gene expression was analyzed using the cytokine/receptor microarrays as before. The transfected IHEKs (Tx) exhibited a marked increase in the number of genes upregulated by HD treatment as compared with their untransfected counterparts (un-Tx). Expression of platelet- and placenta- growth factors and interleukin 8 (IL-8) were rapidly and continuously upregulated over the HD treatment period in Tx while this was true only for IL-8 and prohibitin in un-Tx. Rapid and continuous downregulation was observed for lymphotoxin in Tx. In un-Tx Wnt-2 and vascular endothelial growth factor (VEGF) were found to display the pattern of rapid and continuous downregulation.