Madin-Darby canine kidney (MDCK) cells have a distinctive epithelioid morphology and display several functional and anatomical properties of normal kidney tubule cells. This cell line has been considered ideal for studying cell growth and regulation and for understanding the factors involved in the assembly of epithelial cells into organized multicellular units and tubulogenesis. In this work, we examined the effect of nutritional stress on the morphological and growth characteristics of MDCK cells. Control MDCK cells grew in monolayers but ceased to proliferate after confluence and eventually die. In contrast, nutritionally stressed cells showed continuous multilayered growth, with differentiation and the formation of tubular structures during prolonged culture, as well as enhanced polyploidy. Enhanced fibronectin, actin and vimentin deposition were observed in regions of cell-cell contact in stressed cells. These results indicate that nutritional stress may alter the interactions between extracellular matrix components, including fibronectin, and the cytoskeleton. Such alterations may be important in folding of the epithelial monolayer to form tubular structures.