Cystic fibrosis (CF) is caused by a defect in the cystic fibrosis transmembrane conductance regulator (CFTR) protein that functions as a chloride channel. Dysfunction of the CFTR protein results in salty sweat, pancreatic insufficiency, intestinal obstruction, male infertility and severe pulmonary disease. Most of the morbidity and mortality of CF patients results from pulmonary complications. Differences in susceptibility to bacterial infection and variable degree of CF lung disease among CF patients remain unexplained. Many phenotypic expressions of the disease do not directly correlate with the type of mutation in the Cftr gene. Using a unique CF mouse model which mimics aspects of human CF lung disease, we analyzed the differential gene expression pattern between the normal lungs of wild type mice (WT) and affected lungs of CFTR knockout mice (KO). Using microarray analysis followed by quantitation of candidate gene mRNA and protein expression we identified many-interesting genes involved in the development of cystic fibrosis lung disease in mice. These findings point to distinct mechanisms of gene expression regulation between mice with CF and control mice.