The integrin superfamily of adhesion receptors mediates interactions between cells and the extracellular matrix. Our earlier immunohistochemical analysis showed that normal mammary epithelium expressed high levels of the alpha 2 beta 1 collagen/laminin receptor and intermediate levels of the alpha 5 beta 1 fibronectin receptor. In contrast, malignant cells of adenocarcinoma of the breast exhibited marked diminution or loss of the alpha 2 beta 1 and alpha 5 beta 1 integrins. We have now evaluated the level of alpha 2, alpha 5, and beta 1 integrin subunit messenger (m)RNA by in situ hybridization in adenocarcinoma of the breast. Normal breast ducts and ductules expressed high levels of all three integrin subunit mRNAs. Poorly differentiated lesions expressed low to undetectable levels of alpha 2, alpha 5, and beta 1 mRNA. Well- and moderately differentiated lesions expressed all three subunits at intermediate levels. Thus, decreased expression of the alpha 2 beta 1 and alpha 5 beta 1 integrins in mammary carcinoma is the result of decreased steady-state integrin subunit mRNA levels due to altered expression of the integrin genes.