One of the earliest events leading to cell activation and growth is the hydrolysis of inositol phospholipids producing various membrane signals induced by an interaction between growth factors or hormones with their respective receptors on the cell membrane . To demonstrate the mitogenic action of transferrin, our results show that an addition of transferrin to “serum-deprived” rat hepatoma cells produced a rapid but transient rise in inositol 1, 4, 5-trisphosphate (IP_3) level, and at the same time, an increased intracellular Ca~(2+) activity and a cytoplasmic alkalinization were observed. These signal transduotions further lend support to the mitogenic nature of transferrin. In addition, a possible link between the receptor-mediated endocytosis of transferrin with the generation of intracellular signals is discussed herewith. One of the earliest events leading to cell activation and growth is the hydrolysis of inositol phospholipids producing various membrane signals induced by an interaction between growth factors or hormones with their respective receptors on the cell membrane. To demonstrate the mitogenic action of transferrin, our results show that an addition of transferrin to “serum-deprived” rat hepatoma cells produced a rapid but transient rise in inositol 1, 4, 5-trisphosphate (IP 3) level, and at the same time, an increased intracellular Ca 2+ ) activity and a cytoplasmic alkalinization were observed. These additions are further supported by the mitogenic nature of transferrin. In addition, a possible link between the receptor-mediated endocytosis of transferrin with the generation of intracellular signals is discussed herewith.