Cigarette smoking is strongly associated with the development of lung cancer and chronic obstructive pulmonary disease. In order to investigate the potential mechanisms of smoke toxicity we have performed a transcriptomics study of the effects of whole cigarette smoke on human lung epithelial cells. Primary bronchial epithelial cells from a series of human donors were seeded onto cell culture inserts and grown at an air-liquid interface for 3 weeks to induce mucociliary differentiation. The cells were then exposed to either filtered air, or whole smoke diluted 1/50 or 1/300 in air (smoke/air, v/v) at an air-liquid interface for 1, 6 and 24 hours using an exposure system developed by BAT. These doses of smoke were previously established to be minimally toxic and sub-toxic to the cell cultures. Total RNA was extracted, processed, labelled and hybridised to Affymetrix HG U133 Plus 2.0 arrays. Raw data were scaled using Affymetrix GCOS software and analysed for robust changes using Genespring. Data on genes consistently up-regulated or down-regulated by smoke in all or most of the donor cell lines, intra- and inter-donor variability and a functional interpretation of the response will be presented.