The insulin receptor family in mammals includes the receptors for insulin, insulin-like growth factor I (IGF-I), and the insulin receptor-related receptor (IRR), a receptor whose sequence is homologous to the sequences of the other two receptors but whose ligand is unknown (Fig. 1) (1). Another potential receptor in this family is the receptor for relaxin, a hormone whose structure is related to that of insulin (2). In addition, other members of this receptor family could exist for IGF-I and the highly related IGF-II. Although the cDNA and gene for one receptor which binds IGF-I with high affinity has been isolated (3), several pieces of data suggest that there may be other related IGF receptors. For example, although the receptor expressed from this cDNA had high affinity for IGF-I and IGF-II but almost 1000-fold weaker affinity for insulin (4), several reports in the literature have indicated that there are IGF receptors with a much higher affinity for insulin or a much weaker affinity for IGF-II (5, 6). Some of these studies may have been affected by the presence of hybrid insulin-IGF-I receptors (7). In addition, expression of the apparently same cDNA for the IGF-I receptor in another cell type led to the formation of a receptor which had high affinity for IGF-I and weak affinity for IGF-II when binding studies were performed on whole cells but which bound IGF-I and II almost equally when binding studies were performed in cell lysates (8). In addition, several monoclonal antibodies to the IGF-I receptor were found to stimulate an increase in the affinity of the IGF-I receptor for insulin almost to the level of the insulin receptor (9). These results suggest that the same IGF receptor can bind the IGFs and insulin with different relative affinities depending on the environment of the receptor in the cell membrane. Thus, it is not clear at the present time whether another IGF receptor exists or whether these different binding data can be explained by the present IGF-I receptor interacting with other molecules in different cell backgrounds.