There are two types of Sm/IGF receptors based on results of competitive binding experiments and investigations of receptor structure. The type I receptor preferentially interacts with IGF I rather than IGF II and interacts weakly with insulin. This receptor has a binding subunit of Mr = 130 000 which is disulphide bonded to form larger structures of Mr greater than 300 000. The type II receptor prefers IGF II to IGF I and does not interact with insulin. Its binding subunit is not linked by disulphide bonds to other membrane components (Mr = 260 000 with reduction, 220 000 without reduction). Subunit organization of the type I receptor appears to be similar to that of the insulin receptor but it is unlikely that the insulin and Sm/IGF binding sites are on a common alpha subunit. The type I receptor is down-regulated by IGFs and insulin. A rapid increase in ligand binding to the type II receptor by insulin has been described in intact rat adipocytes. The original idea that an IGF receptor mediates the growth-promoting action of both IGFs and insulin while acute metabolic effects of insulin and IGFs are mediated by the insulin receptor is an oversimplification . There now are clear examples of insulin stimulating growth by acting through the insulin receptor and, conversely, instances of IGF stimulating glucose transport by acting through an IGF receptor. Radioreceptor assays which measure IGF I in preference to IGF II (human placental membrane) and which measure IGF II in preference to IGF I (rat liver and rat placental membranes) have been utilized for clinical measurements of Sm/IGF levels, but are less specific than the respective radioimmunoassays. With the demonstration of Sm/IGF receptors on circulating human mononuclear cells and human skin fibroblasts, it is expected that these systems will be useful for investigations of patients with possible end-organ resistance to Sm/IGF.