The existence of insulin-like growth factors (IGFs) in blood was fi rst recognized by Wiliam D. Salmon Jr. and Wiliam H. Daughaday in 1956. Examining the role of pituitary-regulated growth-stimulating substances, these authors demonstrated that a growth hormone (GH) dependent factor in serum could stimulate labeled sulfate (35SO4) incorporation into chondroitin sulfate (cartilage) in vitro. In line with their fi ndings, Salmon and Daughaday initially designated this factor as ‘sulfation factor’. Comparative studies were also performed in vivo. Hypophysectomy of rats markedly reduced labeled sulfate incorporation into chondroitin sulfate of epiphyseal cartilage, whereas injections of pituitary extracts and purifi ed bovine GH effectively restored 35SO4 incorporation. The observations that the direct effect of bovine GH on costal cartilage was minimal, whereas serum from hypophysectomized rats treated with bovine GH stimulated 3H-thymidine incorporation into cartilage led to the postulation that GH utilized the intermediary substance sulfation factor.