Aberrant regulation of the immune system can lead to the development of autoimmune diseases such as myasthenia gravis. Autoantibodies against the nicotinic acetylcholine receptor (AChR) are found in the serum of myasthenia gravis patients and trigger a reduction of AChR at the muscle endplate resulting in increased muscle fatiguability. It is possible that the autoimmune response results from altered idiotype anti-idiotype network interactions. Here we have used a monoclonal anti-AChR antibody (ACR-24, gamma 1, kappa) in an enzyme-linked immunoabsorbent assay (ELISA) to measure anti-AChR immunoglobulin in human sera. In this assay, ACR-24 is attached to microtitre plates followed by the addition of solubilized human AChR which is bound by the immobilized ACR-24. However, during the development of this assay, it was observed that certain myasthenic patients appeared to have antibodies which bound to ACR-24 alone. This unexpected finding suggested that we had discovered naturally occurring anti-idiotype antibodies in myasthenic sera.