Breast milk contains various biologically active factors including, hormones, peptide growth factors, and cytokines. Epidermal growth factor (EGF) and insulinlike growth factor-I (IGF-I) are two of the major milk-derived peptide growth factors. Colostrum contains higher levels of these growth factors than mature milk does, and, these factors are relatively resistant to proteolysis and stable in the G-I tract. There are specific receptors found in G-I mucosa. Luminal EGF and IGF-I stimulate growth and development of gastrointestinal tract. Intestinal epithelial Caco-2 cells are a good model for studying physiological roles of exogenous growth factors in the G-I development. Effect of EGF and IGF-I on proliferation, differentiation, and IGF-binding protein (IGFBP) production of intestinal Caco-2 cells were studied. Both EGF and IGF-I increased cell proliferation in dose dependent manner. The number of IGF-I receptors on Caco-2 cells increased after differentiation, in contrast to EGF binding which was reported to decrease. Caco-2 cells produced at least three IGFBPs, namely IGFBP-2, -3, and -4. The profile of these IGFBPs varied with differentiation. Secretion of IGFBP-2 and -3 increased with differentiation, but IGFBP-4 diminished. IGF-I stimulated mainly IGFBP-3 production, while EGF stimulated predominantly IGFBP-4. The effects of IGF-I and EGF on IGFBP secretion diminished with increasing cell differentiation. Thus, the interaction between intestinal epithelial cells and extrinsic growth factors are complex and the stage of differentiation is an important determinant of this phenomenon.