Insulin receptor beta-subunit autophosphorylation, the first event occurring after insulin binding, plays a crucial role in modulation of receptor-associated kinase activity towards exogenous substrates and possibly in the transmission of biological signals of insulin. Receptor autophosphorylation strongly depends on insulin receptor occupancy. Till now the effects of receptor phosphorylation on insulin binding itself have not been clarified. In the present report we demonstrate the absence of any feedback mechanism by which insulin receptor activation by phosphorylation affects binding affinity of insulin receptor itself.