Transforming growth factor-β (TGF-β) inhibits the growth of endothelial cells derived from various sources, including human umbilical vein, bovine aorta, and rat heart. Long-term exposure of rat heart endothelial cells to TGF-β also induces dramatic changes in morphology that are characteristic of senescent cells. These changes are accompanied by a decrease in the number of high-affinity receptors for epidermal growth factor (EGF), with almost no change in total receptor number. Additionally, the EGF-induced expression of specific competence genes (c- myc, JE, KC) is decreased, whereas the induction of c- fos gene expression by EGF is unaltered by TGF-β treatment. These data suggest that growth inhibitors such as TGF-β may act by altering the cell's response to growth-stimulatory factors.