Background Activated T and B lymphocytes are the predominant inflammatory cells in atopic eczema (AE) lesions. Mycophenolic acid, the active form of mycophenolate mofetil (MMF), blocks the proliferative responses of T and B lymphocytes. Objectives In this pilot study, we examined the efficacy of MMF (CellCept®, Hoffman La Roche, Grenzach-Wyhlen, Germany) in severe AE. Methods Ten patients with severe AE (severity index > 50) according to the Severity Scoring of Atopic Dermatitis (SCORAD) index were treated with oral MMF at an initial dose of 1 g daily during the first week and 2 g daily for a further 11 weeks. Laboratory examination including full blood count, lymphocyte subset analysis, serum immunoglobulins (IgE, IgG, IgM, IgA), total bilirubin, alkaline phosphatase, aminotransferases, lactate dehydrogenase and creatinine was performed every 2 weeks. Additionally, interleukin (IL)-10 and interferon (IFN)-γ in serum were measured. Results None of the 10 patients who received MMF discontinued the trial because of lack of efficacy or adverse events. Compared with the baseline, the median scores for disease severity (SCORAD index) improved by 68% during treatment with MMF. The median serum IgE level decreased significantly, from 10,300 kU L−1 before treatment to 7830 kU L−1 after 12 weeks. MMF induced a significant increase in the T-helper (Th)-1-related cytokine IFN-γ and a significant decrease in IL-10, mainly produced by Th2 cells. Conclusions The present study demonstrates that oral MMF at a dose of 2 g daily is an effective, safe and well-tolerated immunosuppressive therapy for severe AE in adults.