Antibodies generated against two synthetic peptides corresponding to two defined regions on the transforming protein of Rous sarcoma virus, pp60src, interact specifically with the epidermal growth factor (EGF)-receptor kinase. An antibody directed against a synthetic peptide corresponding to the major phosphorylation site of pp60src interacts specifically with EGF receptor and immunoprecipitates a functional EGF-receptor kinase. The second antibody, which binds close to a region on the src molecule that is required for its kinase activity, also binds to EGF-receptor kinase and prevents the autophosphorylation of the receptor molecules. Neither antibody binds to intact cells, but they do recognize various forms of the solubilized receptor. It is concluded that at least two cytoplasmic domains of the EGF receptor are antigenically and presumably also structurally related to specific domains on pp60src.