So far, there are no satisfactory drugs with a consistent corticosteroid(CS)-sparing effect in patients with severe asthma. Mycophenolate mofetil (MMF) is a powerful and relatively specific inhibitor of lymphocyte proliferation and recruitment, which induces apoptosis of activated T-cells. We present 2 patients with CS-dependent asthma treated with MMF. The patients were on high doses of inhaled CS, long-acting β-agonists and long-term oral CS. Baseline FEV1 (%predicted) in the previous year varied between 35 and 70% in the first and between 47 and 69% in the second patient. Prednisone couldn't be reduced below 20mg/d without consecutive exacerbations. Given a symptomatic osteoporosis in both patients alternative therapies were considered. Cyclophosphamide (1g/m iv pulses for 4m) in the first patient showed no convincing CS-sparing effect. The other patient received methotrexate (25mg/w sc for 16m). Although this regimen allowed to reduce prednisone to ≥10mg/d, methotrexate had to be discontinued due to gastrointestinal side effects. In both patients MMF was started (initially 2x1g/d). Leucocyte count and serum PCR for cytomegalovirus were monitored. Prednisone could subsequently be tapered to 10mg/d. Dyspnea-score remained stable (ATS II) and FEV1 increased from 43 to 63% and 58 to 68%, respectively. The treatment was well tolerated. We conclude that MMF could be an effective and relatively safe CS-sparing agent in patients with CS-dependent asthma. A larger case series seems to be warranted.