This study reports our preliminary experience with mycophenolate mofetil (MMF)-based immune suppression after lung transplantation. Thirteen patients (group 1) received MMF as primary therapy immediately after transplantation. Use of MMF was associated with a linearized rate of 0.85 episodes of acute rejection per 100 patient days during the first 3 months after transplantation, as compared with rates of 1.49 and 1.38, observed in two groups of historical control subjects (p = .094 and p = .053, respectively). Rejection rates after the first 3 months were not lower than in historical control subjects. Nine additional patients were switched from azathioprine to MMF because of recurrent episodes of high-grade acute rejection (group 2). In this group, the linearized rate of acute rejection episodes declined significantly (p = .004) after initiation of MMF therapy. These data suggest a potential role for MMF in reducing the rate of acute rejection episodes after lung transplantation.