During development, the proximal and distal regions of respiratory tract undergo distinct processes that ultimately give rise to conducting airways and alveoli. To gain insights into the genetic pathways differentially activated in these regions when branching morphogenesis is initiating, we characterized their transcriptional profiles in murine rudiments isolated at embryonic (E) day 11.5. By using oligonucleotide microarrays, we identified 83 and 128 genes preferentially expressed in branching and non-branching regions, respectively. The majority of these genes (85%) had not been previously described in the lung, or in other organs. We report restricted expression patterns of 22 of these genes were by in situ hybridization. Among them in the lung potential components of the Wnt, TGF beta, FGF and retinoid pathways identified in other systems, and uncharacterized genes, such as translocases, small GTPases and splicing factors. In addition, we provide a more detailed analysis of the expression pattern and regulation of a representative gene from the distal (transforming growth factor, beta induced) and proximal (WW domain-containing protein 2) regions. Our data suggest that these genes may regulate focal developmental events specific of each of these regions during respiratory tract formation.