Mycophenolate mofetil (MMF) is an immunosuppressive agent that exerts relatively selective antiproliferative effects on T and B lymphocytes. Efficacy has been demonstrated in large-scale randomised studies, but the use of MMF is complicated by gastrointestinal upset and is associated with an increased incidence of tissue-invasive cytomegalovirus (CMV) disease. The gastrointestinal tract is a well recognised site for invasive CMV disease, and it has therefore been hypothesised that the abdominal pain commonly seen with MMF is related to CMV infection. This has only been tested in a single small uncontrolled study, where abdominal pain was associated with the presence of CMV on endoscopic biopsy. In contrast, the toxicity profile in 85 patients with psoriasis who had received relatively high dosages of mycophenolic acid, the active moiety of MMF, for up to 13 years showed that the incidence of gastrointestinal upset fell dramatically over time. We can find little evidence that CMV disease explains the gastrointestinal adverse event profile associated with MMF, and instead support the contention that high local concentrations of MMF have a direct toxic effect on cells of the small intestine. We do not recommend any changes to current policy on CMV prophylaxis in patients receiving MMF, although we recognise that some severe gastrointestinal adverse effects may be CMV-associated. The use of trough plasma concentration monitoring, divided doses and a gradually increasing dosage schedule may be of value in limiting toxicity.