OBJECTIVES: Standard therapies against inflammatory rheumatic diseases consist of immunosuppressive drugs with high toxicities and many side effects. Except in the treatment of systemic lupus erythematosus with renal involvement, controlled studies with mycophenolate mofetil (MMF) are lacking in other autoimmune and inflammatory systemic diseases. Here we describe our clinical experience with MMF in several unusual indications. METHODS: We collected data including serological findings, adverse events and response to treatment in eleven patients with autoimmune diseases including systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), polymyositis (PM), diffuse systemic sclerosis that were treated in our rheumatology unit. RESULTS: Our results show remission in ten patients with minimal side effects and reduced prednisone dosage. The median dose of MMF was 2 g per day. Adverse events were limited, with one case of leucopenia, one tachycardia and one colitis. One patient definitively stopped the treatment because of side effects. CONCLUSIONS: MMF seems to be a very powerful and attractive alternative medication in the treatment of immune-mediated inflammatory diseases. The good tolerance and safety profile makes it an excellent therapeutic option permitting a global reduction of corticosteroids doses.