The insulin-like growth factors IGF-I and -II have effects on metabolism, growth, proliferation and differentiation in many tissues and cell types 1 and are therefore important modulators of multiple aspects of physiology. IGF actions are largely mediated via the type 1 IGF receptor, 2 though both peptides, particularly IGF-II, can bind to a second receptor known as the type 2 IGF/mannose-6-phosphate receptor. Access to these receptors is controlled by a family of six highly speci®c binding proteins (IGFBPs 1±6 1 ). Originally, the IGFBPs were thought of as IGF inhibitors, since their af®nity for ligand is substantially higher than that of the receptors. More recently however, it has become apparent that modi®cation of the binding proteins, for example proteolyis, phosphorylation or association with extracellular matrix, can in¯uence IGFBP af®nity for IGF and therefore IGF bioavailability and function.