TGF-beta strongly inhibits the mitogenic effect of growth factors such as insulin-like growth-I (IGF-I) on thyroid follicular cells. To study the mechanism of this inhibiting action, the effect of TGF-beta 1 on tyrosine phosphorylation of 175kDa substrate induced by IGF-I was investigated in FRTL-5 thyroid epithelial cells. After treatment with TGF-beta 1, tyrosine phosphorylation of 175kDa protein induced by IGF-I was inhibited in parallel with the degree of the inhibition of cell proliferation. However, TGF-beta 1 had no effect on tyrosine phosphorylation of 120kDa substrate. These results suggest that TGF-beta 1 blocks the mitogenic signal of IGF-I by inhibiting the tyrosine phosphorylation of 175kDa substrate in FRTL-5 cells.