We used RNA-RNA in situ hybridization to study expression of the human CC10 gene in morphologically normal and atypical areas of 32 non-neoplastic lung specimens resected from 26 non-small cell lung cancer patients. We scored strong, moderate or weak levels of CC10 mRNA expression in 3 distinct lung compartments. In morphologically normal lungs, strong and moderate levels of CC10 mRNA were observed in bronchioli and bronchi, respectively, but the expression was rarely observed in the alveolar region. Distinct alterations in CC10 mRNA expression were noted in specific histologic abnormalities within bronchi and the alveolar region. CC10 hybridization signal decreased markedly in bronchi containing diffuse goblet cell hyperplasia or squamous metaplasia, while CC10 mRNA expression remained unchanged in bronchi with basal cell hyperplasia or focal goblet cell hyperplasia. Bronchiolar CC10 mRNA levels remained unchanged in sections containing abnormalities elsewhere. Interestingly, in alveoli with bronchiolization of the alveoli, high levels of CC10 mRNA were observed. These regions also contained strongly stained keratin 14-positive cells, which may indicate a concurrent metaplastic process. In lungs with morphologic atypias, no correlation was found between abnormalities detected in bronchi and alveoli from the same lung. A comparison of mRNA expression and clinicopathologic features demonstrated that the amount of histologic abnormalities increased with smoking history (pack years); however, no correlation between CC10 mRNA expression and sex, age or smoking history was found.