Negative control of cell proliferation is important in regulating a wide range of biological processes. The transforming growth factor-fl (ICE-β) family shows multiple functions on cell growth and differentiation in a tissue/cell type-specific manner. In epithelial cells, TGF-β1 causes the growth arrest, in parallel with the accumulation of hypophosphorylated retinoblastoma susceptibility (Rb) gene product, suggesting that TGF-β1-induced growth arrest is mediated by Rb gene product. Recently, evidence is available that TGF-β-mediated growth arrest is due to block of phosphorylation of Rb gene product by Rb kinases. Rb gene product may be a primary target for action of TGF-β1 but additional factors or pathways may also be involved in its regulating mechanisms of cell growth.