In the healthy individual, host defence mechanisms usually lead to the rapid clearance of bacteria from the respiratory tract. However, in the cystic fibrosis (CF) patient several opportunistic pathogens, in particular Pseudomonas aeruginosa frequently colonise the lungs inducing chronic infections in the respiratory tract. In response to the infection the CF host elicits a neutrophil dominated inflammatory response which damages the airway epithelium leading to lung degeneration. This study aims to investigate CF host gene transcriptome changes in response to infection compared to control CF cells. To identify the genes implicated in the immune and subsequent inflammatory response to infection by P. aeruginosa we cultured a Cystic Fibrosis Tracheal Epithelium (CFTE29o-) cell line for co-culture with a wild-type strain of P. aeruginosa, PAO1. Co-cultures were performed for a duration of 3 hours, with a multiplicity of infection (M.O.I) of bacterial cells to host cells of 50:1 (Ichikawa et al. 2000). The cell monolayer was harvested and messenger Ribosomal Nucleic Acid (mRNA) was isolated for comparative analysis. Host transcriptional profiles were assessed in triplicate using MWG Human 10K oligonucleotide arrays, where each sample was differentially labelled and hybridised to a microarray. Analysis of array images was performed using Imagene® and analysis of the data was carried out using Genesight® software. Of the 9850 genes on the arrays, 2% were found to be reproducibly differentially transcribed following infection in the co-cultured sample compared to the unco-cultured control sample. The inflammatory cytokine, interleukin 8 (IL-8) was found to be differentially transcribed by 6 ± 0.15 fold following infection in our study. Standard deviation was determined, where n=3. While the overexpression of IL-8 is well documented in literature we also found that the expression of another CXC chemokine, growth-related oncogene-alpha (CXCL1) was induced following infection, with an average increase of 3 ± 0.25 fold. Additionally regulatory gene transcription was increased including, the activating transcription factor 4 (ATF4) by 3 ± 0.06 fold. Having identified novel genes of significant change we are currently validating the gene array results by quantative RT-PCR using samples isolated following co-culture. In conclusion, these experiments demonstrate that there are significant differences in the gene transcription level in CFTE29o- following co-culture with PAO1 compared to control uninfected CFTE29o- cells and help to understand host defence mechanisms that occur following infection.