The membrane receptor for epidermal growth factor is a transmembrane protein composed of an EGF-binding domain and a cytoplasmic kinase domain, connected by a single hydrophobic stretch. The binding of EGF to the extracellular domain activates the cytoplasmic kinase function even in highly purified preparations of EGF receptor, suggesting that the activation occurs exclusively within the EGF receptor moiety. The experiments presented indicate that self-phosphorylation of the EGF receptor is dependent on the concentration of the receptor and that antibodies which cross-link the receptor molecules stimulate self-phosphorylation and increase the affinity of EGF towards the receptor. Moreover, immobilization of the EGF receptor on various solid matrices prevents EGF from activating the kinase function. These results are compatible with an intermolecular activation of the tyrosine kinase followed by an intramolecular self-phosphorylation process. An allosteric aggregation model is formulated as a framework to these and other regulatory responses attributed to the EGF receptor complex.