Uteroglobin (UG) is a hormonally regulated secretory protein produced in the lung and urogenital system of rabbits. It is homologous to rat and human Clara cell 10 kD protein (CC10); however, there are significant differences in the tissue-specific expression between these species. Mouse CC10 (mCC10) protein has been less well characterized. In this study, we cloned and sequenced the cDNA encoding the mCC10 protein. The mouse cDNA showed 90, 52, and 51% amino acid homology to rat and human CC10 and rabbit UG cDNA, respectively. The cellular and tissue-specific expression of mCC10 was examined in adult and developing mice. Endogenous mCC10 expression was compared with transgenic mice expressing a fusion gene of the rabbit 3.3 kb UG promoter linked to human growth hormone (hGH) as an easily detectable marker. Northern blot analysis detected mCC10 mRNA only in the lung. hGH mRNA was detected in the lung in levels similar to the endogenous mCC10 transcripts. However, it was also present in trace quantities in the uterus and ovary of normal adult female mice and in the epididymus of adult male mice. hGH and mCC10 proteins were identified in the trachea and lung, where they were localized to Clara cells. Ultrastructurally, hGH was present in secretory granules in the Clara cell cytoplasm and appeared to be secreted into the airways. hGH was initially detectable in 16 day gestation developing mice; however, CC10 was not detectable until the eighteenth day of gestation. We have created an attractive model for comparing the cis-acting DNA elements governing the interspecies variation in tissue-specific expression of CC10.