BACKGROUND: In utero environmental tobacco smoke (ETS) exposure exacerbates initial lung responses of adult mice to ovalbumin (OVA), a common allergen in rodent models of allergicasthma. OBJECTIVE: We tested the hypothesis that in utero ETS exposure alters expression of genes (including asthma-related and inflammatory genes) in the lungs of adult mice and that this differential expression is reflected in differential respiratory and immune responses to nontobacco allergens. METHODS: Using Affymetrix Mouse Genome 430 2.0 arrays, we examined gene expression changes in lungs of BALB/c mice exposed to ETS in utero, OVA, or saline aerosol at weeks 7-8, and OVA sensitization and challenge at weeks 11-15. Data sets were filtered by transcript p-value ([less than or equal to] 0.05), false discovery rate ([less than or equal to] 0.05), and fold change ([greater than or equal to] 1.5). Differential expression of selected genes was confirmed by polymerase chain reaction (PCR). RESULTS: Genes differentially expressed as a result of in utero ETS exposure are involved in regulation of biological processes (immune response, cell proliferation, apoptosis, cell metabolism) through altered cytoskeleton, adhesion, transcription, and enzyme molecules. A number of genes prominent in lung inflammation were differentially expressed on PCR but did not pass selection criteria for microarray, including arginase (Arg1), chitinases (Chia, Chi3l3, Chi3l4), eotaxins (Ccl11, Ccl24), small proline-rich protein 2a (Sprr2a), and cytokines (Il4, Il6, Il10, Il13, Tnfa) . CONCLUSION: The differential lung gene expression reported here is consistent with previously reported functional changes in lungs of mice exposed in utero to ETS and as adults to the non-tobacco allergen OVA. KEY WORDS: allergy, asthma, environmental tobacco smoke (ETS), gene regulation, in utero, inflammation, lung, ovalbumin. Environ Health Perspect 115:1757-1766 (2007). doi:10.1289/ehp.10358 available via http://dx.doi.org/ [Online 19 September 2007], The incidence of asthma and allergy has increased dramatically during the past 30 years, primarily in industrialized countries (Eder et al. 2006). Although improved availability and quality of medical care [...]