Populations of alveolar macrophages recovered from the lower respiratory tract secrete fibronectin, a multi-functional glycoprotein capable of influencing cell migration, attachment, differentiation, and proliferation. Using in situ hybridization of 35S-labeled antisense and sense RNA fibronectin probes, the present study demonstrates that most, but not all, normal alveolar macrophages contain fibronectin mRNA transcripts, and that among those macrophages expressing this gene, the relative amount of fibronectin mRNA transcripts varies from cell to cell. Interestingly, while 66 +/- 3% of normal alveolar macrophages contain fibronectin mRNA transcripts, this is increased to 82 +/- 2% (P less than 0.01) of alveolar macrophages recovered from the lungs of individuals with idiopathic pulmonary fibrosis (IPF), a chronic inflammatory disorder associated with exaggerated amounts of fibronectin in the lower respiratory tract. Furthermore, of the macrophages expressing the fibronectin gene, those from IPF patients contain more fibronectin mRNA transcripts than those from normals. Consistent with this observation, evaluation of tissue samples from IPF patients demonstrated that of all cells present, alveolar macrophages showed the greatest numbers of fibronectin mRNA transcripts per cell. These observations demonstrate that there can be marked cell-to-cell variation in the expression of the gene for a macrophage product such as fibronectin, suggesting that there are processes that modulate similar cells in the same anatomic compartment to vary their expression of the same gene.