Anti-cytokine antibodies (Abs) play an important role in the regulation of the immune response, both under normal conditions and in several autoimmune and neoplastic disorders. In the present study, we have investigated the occurrence and the clinical significance of natural neutralizing Abs (NAbs) against interferons (IFNs) alpha (α), beta (β) and gamma (γ), as detected by bioassay, in 52 patients with myasthenia gravis (MG), and 43 sex-and age-matched healthy individuals. Patients showing titres≥ 1.3 Log t1/10, confirmed in 2 consecutive samples collected two months apart, were considered positive. NAbs against any of the IFNs were not detected in healthy subjects. Of the 52 MG patients, 11 (21.1%) had NAbs against IFNα and three (5.8%) had NAbs against IFNβ. None of these patients was found to be positive for NAbs against IFNγ. Of the patients positive for NAbs against IFNα, eight (15.4%) had NAbs at titres≥ 2 Log t1/10. A positive association was observed between high titres of NAbs and the presence of thymoma. These data suggest the presence of a generalized activation of the humoral response in MG.