Bianca Conti-Tronconi, Socrates Tzartos, and Jon Lindstrom* abstract: Binding of monoclonal antibodies to Torpedo californica acetylcholinereceptor monomers solubilized in Triton X-100 was studied by centrifugation on sucrose gra-dients. Antibodies to a subunits were of two types. One type formed complexes of one antibody and one receptor monomer, independent of antibody/receptor ratio. We conclude that the binding sites for these antibodies are oriented on the two a subunits per monomer in such a way that each could be bound by one of the two binding sites of a single immunoglobulin molecule. Most antibodies were of this type. The other type of monoclonal antibody formed complexes of several sizes, including antibody cross-linked receptors, depending on the ratio of antibody toreceptor. We conclude that the binding sites for these antibodies are oriented in such a way that the two a subunits per monomer could not be cross-linked by a single antibody molecule. A monoclonal antibody of this type raised againstElectrophorus electricus receptor was used to show that this receptor also has two a subunits per monomer. This antibody cross-reacted with receptor from fetal calf muscle and was able to induce antigenic modulation of receptor