This study demonstrates that perturbation of the fibronectin receptor (FNR), a member of the integrin family of adhesion receptors, can stimulate growth of non-transformed epithelial cells but not of transformed epithelial cells. Using the non-adherent cell line FA-K562 we demonstrate that growth stimulation via FNR ligands occurs rapidly and independently of any effects on cell adhesion. Low valence FNR ligands such as glycine-arginine-glycine-aspartate-serine (GRGDS) are the most potent stimulators of the cell cycle regulatory kinase cdc2. Partial synchronization and Western blotting studies suggest that GRGDS affects cdc2/cyclin A complexes in cells in S/G2 phase of the cell cycle. These studies suggest that FNR-mediated growth control appears to be a common feature of transformation. These data suggest that the FNR may be physiologically important in growth control, especially in the presence of low valence, proteolytic degradation fragments of FN. Furthermore, escape from FNR-mediated growth control may be a common feature of transformation.