The use of mycophenolate mofetil (MMF) for prophylaxis of aGVHD and/or for treatment of acute or chronic GVHD is increasing. However, the benefit of MMF as an alternative to commonly used immunosuppressive agents still needs to be assessed. We ran a retrospective study on 21 consecutive patients (median age, 36 years; range, 20-63) with aGVHD or extensive cGVHD following related (17) or unrelated (4) matched donor SCT (BM, 16; PBSC, 5) who received MMF (2 g/day) because of intolerance to or failure of CsA-containing combinations. Four of the six patients with aGVHD responded, and the response rate was 69% in cGVHD patients. We observed neither significant differences in terms of response rate for skin, liver and bowel nor dissociated response in cases of multiple organ involvement (67% of the patients). Response was the same for lichenoid and sclerodermatous skin cGVHD subtypes. No adverse effects, except diarrhea (three patients), were observed. However, 22 opportunistic or serious viral or bacterial infections occurred in 10 patients. Analysis of trough plasma levels showed a trend for a higher mean MPA concentration in patients responding to MMF. Our study highlights the high risk of infectious complications induced by the administration of MMF, an otherwise efficient and well-tolerated treatment for GVHD.