Patient description: The patient is a 35-year-old woman with myasthenia gravis, class IIa. She complains of diplopia and fatigue and weakness that affects mainly her upper limbs. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She takes pyridostigmine 60 mg three times a day. But she still has some symptoms that interfere with her job. She is a research coordinator and has 3 children. Her 70-year-old father has hypertension. She does not smoke or use illicit drugs. She drinks alcohol occasionally at social events. Her physical exam and lab studies were not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy

Clinical trial eligibility criteria: eligible ages (years): 25.0-80.0,  Stiff Person Syndrome Stiff Person Syndrome with elevated anti-GAD antibody titers. Between 25 to 80 years of age. Willingness to stop IVIg therapy 6 weeks prior to Rituximab/Placebo treatment and for the remainder of the study. [If receiving IVIg, patients will be allowed to receive the ongoing non-immunosuppressive drugs used to treat SPS including Diazepam, Neurontin or Baclofen. The dose of these drugs will remain stable throughout the study and unchanged for 6 weeks prior to enrollment.] Willingness and legal ability to give and sign informed study consent. Willingness to travel to NIH for scheduled protocol studies and treatment. Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for six months after completion of treatment. Adequate bone marrow, renal, and liver function: ANC greater than 1000/mm(3), BUN/Cr in normal range for age. Patients with Diabetes (Type II) will be allowed to participate because up to 40% of SPS patients have Diabetes. Patients with a history of controlled epilepsy will be allowed to participate because up to 5% of SPS patients have mild epilepsy which is easily controlled  Immunosuppressive drug therapy for SPS at the time of or 6 weeks prior to enrollment and for the remainder of the study. Specifically, candidates may not be taking prednisone, cyclosporine, tacrolimus, azathioprine, mycophenolate mofetil, anti-lymphocyte agents, cyclophosphamide, methotrexate, or other agents whose therapeutic effect is immunosuppressive. Any medical or social condition that precludes follow-up visits. Any active malignancy or any history of a hematogenous malignancy or lymphoma. Patients with primary, cutaneous basal cell or squamous cell cancers may be enrolled providing the lesions are treated prior to enrollment. History of a coagulopathy or patients requiring anticoagulation. Any history of cardiac insufficiency, major vascular disease, or symptomatic coronary artery disease. Patients with cardiomyopathy grade III or IV by the New York Heart Classification will be excluded from this study. Systemic edema or pulmonary edema. Chronic and severe symptomatic hypotension (SBP less than 100 mmHg). Chronic liver disease or alcoholism. Any condition, including active infections, that would likely increase the risk of protocol participation or confuse the understanding of the data. Pregnancy. Serum pregnancy test will be performed and must be negative in all women of childbearing potential enrolled in the study. History of active psychiatric disorder that may interfere with participation in the study (AT Hemoglobin: less than 7.0 gm/dL. Platelets: less than 100,000/mm. AST or ALT greater than 2.5 x Upper Limit of Normal unless related to primary disease. Positive Hepatitis B or C serology (Hep Surface antigen and Hep C hepatitis C antibody). Positive HIV