We have investigated the expression of integrin chains by human renal epithelial cells during in vivo renal differentiation and in vitro cell culture on different extracellular matrices. Using the immunoperoxidase technique to visualize the binding of monoclonal antibodies to different integrin chains in fetal and adult kidneys, we found a change during development from alpha 1 beta 1, alpha 3 beta 1, and alpha 4 beta 1-positive blastemal cells to alpha 2 beta 1, alpha 3 beta 1, and alpha 6 beta 1-positive epithelial cells. The pattern of integrin expression correlates with the presence in the extracellular matrix of the appropriate ligands. In in vitro cell culture experiments, renal epithelium expressed alpha 3 and alpha 5 integrins on all extracellular matrices. Integrins alpha 2 and alpha 6 were found only in cells grown on a laminin-containing substratum. Fibronectin and alpha 5 integrin co-localized on the ventral surface of cells grown on a laminin substratum and at the periphery of cells on glass coverslips. These results suggest that there is a close relationship between integrin alpha chain usage and the presence of appropriate ligands in the extracellular matrix.