We describe a 48-year-old woman with seronegative myasthenia gravis (MG) and high-titer of anti-MuSK antibody. She had severe bulbar and respiratory weakn ess with minimal limb weakness for 2 years. Her disease responded poorly to all the conventional immunosuppressive regimens. Treatment with immunoablative dose of cyclophosphamide led to dramatic and sustained remission of her symptoms. Hig h-dose cyclophosphamide is an effective alternative in patients with unusually refractory disease. We describe a 48-year-old woman with seronegative myasthenia gravis (MG) and high-titer of anti-MuSK antibody. She had severe bulbar and respiratory weakness with minimal limb weakness for 2 years. Her disease was poorly to all the conventional Immunosuppressive regimens. Treatment with immunoablative dose of cyclophosphamide led to dramatic and sustained remission of her symptoms. Hig h-dose cyclophosphamide is an effective alternative in patients with unusually refractory disease.