AbstractCompetitive binding experiments from a number of laboratories showed that IGF receptors are distinct from insulin receptors, and that there are two types of IGF receptors based on their relative affinities for IGF-I and IGF-II and whether or not they bind insulin (reviewed in Rechler and Nissley, 1985). Later, affinity crosslinking experiments provided a physical basis for the two IGF receptor subtypes. The receptor which preferred IGF-II over IGF-I and did not bind insulin, was a large 250 kDa species with no apparent subunit structure (Fig. 1). The receptor which prefered IGF-I over IGF-II and bound insulin with low affinity had a binding sub-unit of 130 kDa after reduction of disulfide bonds. Biosynthetic labeling experiments demonstrated a 95 kDa beta subunit addition to the 130 kDa alpha subunit (Fig. 1). The heterotetrameric IGF-I receptor (a,&was therefore very similar to the insulin receptor, and the case for similarity was increased when the beta subunit was found to be auto-phosphorylated in response to IGF-I. Molecular cloning of the IGF-I receptor confirmed that the IGF-I receptor and the insulin receptor areclosely related structures (Ullrich et al., 1986).