Chemical-induced allergy continues to be an important occupational health problem. Despite decades of investigation, the molecular mechanisms underlying chemical-induced hypersensitivity and irritancy remain unclear because of the complex interplay between properties of different chemicals and the immune system. In this study, gene expression induced by toluene diisocyanate (TDI, a primarily IgE-inducing sensitizer), oxazolone (OXA, a cell-mediated hypersensitivity inducing sensitizer), or nonanoic acid (NA, a non-sensitizing irritant) was investigated using gene arrays. Female BALB/c mice were dermally exposed on the ears once daily for 4 consecutive days. On day 5, the lymph nodes draining the exposure sites were collected and used for RNA extraction and subsequent hybridization to Affymetrix Mu6500 oligonucleotide arrays. Of the 6519 genes on the arrays, there were 44, 13, and 51 genes in the TDI-, OXA-, and NA-exposed samples, respectively, that displayed a minimum of twofold change in expression level relative to the vehicle control. There were 32, 19, and 19 genes that were differentially expressed (with a minimum of twofold change) between TDI and OXA, TDI and NA, OXA and NA, respectively. The differentially expressed genes include immune response-related genes, transcriptional factors, signal transducing molecules, and Expressed Sequence Tags. Based on the gene array results, candidate genes were further evaluated using RT-PCR. There was only about 47% concordance between the gene array and RT-PCR results.