Structural and functional analyses of several integrin heterodimers were performed in non-small-cell lung cancer (NSCLC) and small cell lung cancer (SCLC) cell lines. The expression of β1, β3, β4, and β5 heterodimers was evaluated at protein and mRNA levels. By flow cytometry and immunoprecipitation experiments we demonstrate that NSCLC cells (A549 adenocarcinoma and DG3 large cell carcinoma) coexpress integrin heterodimers composed of β1, β3, β4, and β5 subunits, whereas SCLC cells (AE2 and H69) express only β1 integrin heterodimers. Northern blot experiments confirmed immunochemical analysis: SCLC cells in contrast to NSCLC cells express only the mRNA coding for the β1 subunit. These data indicate that in lung carcinoma cells the diversity in the integrin repertoire depends upon differential gene expression. The functionality of integrin receptors has been studied using antibody blocking experiments. Data reported demonstrate that the α6β1 integrin is a laminin receptor in either SCLC or NSCLC cells. An antibody to the β4 subunit partially inhibits the adhesion of adenocarcinoma cells to laminin but does not block laminin adhesion of large cell carcinoma cells, even though α6β4 complexes are expressed on both cell types. Two antisera to vitronectin receptors inhibit the adhesion of NSCLC cells to both vitronectin and fibronectin. The same antisera inhibit the adhesion of SCLC cells only to laminin, indicating that the αvβ1 integrin might function in these cells as laminin receptor.