Insulin-like growth factors (IGF) I and II are peptide hormones that regulate cellular proliferation and differentiation. Most circulating IGFs exist in 130-150 kDa ternary complexes containing IGF-Binding Protein-3 (IGFBP-3) and an 85 kDa glycoprotein, the acid-labile subunit (ALS). IGFBP-3 is one of six IGFBPs that, by binding IGF peptides, prolong their half life and maintain the IGF reservoir. IGFBP-3 is found in body fluids as multiple 40-50 kDa forms as a result of differential glycosylation. The expression of IGFBP-3 in many tissues suggests that it locally modulates the autocrine/paracrine action of IGF peptides. IGFBP-3 binding to fibrinogen may be important for wound healing, since this concentrates IGF-I at wound sites and lowers the affinity of IGF-I for IGFBP-3. In addition, retinoic acid-induced IGFBP-3 expression inhibits the growth promoting effects of IGF-I in breast cancer cells. This may link the retinoid and IGF systems in cell growth regulation and explain how the loss of retinoic acid receptor β leads to breast cancer progression. Thus, IGFBP-3 maintenance and regulation of IGF activity in various tissues may have diverse physiological roles.