RS-61443 (mycophenolate mofetil) inhibits a key enzyme of the de novo synthesis of purine nucleotides in T and B lymphocytes. The purpose of this study was to evaluate the efficacy of RS-61443 in patients with refractory renal allograft rejection. Patients eligible for the study had previously undergone anti-rejection therapy with high-dose steroids or OKT3 monoclonal antibody. All rejection episodes were proven by renal biopsy. Successful rescue was achieved in 52 (69%) patients. Rescue was more successful when patients were entered with a creatinine of 4 mg/dL or lower (79%), versus a 52% rescue rate in patients entered with a creatinine of 4 mg/dL or above. Major side effects were predominantly gastrointestinal, but there was no overt nephrotoxicity, hepatotoxicity, or bone marrow suppression. The overall infection rate was 40%, with the spectrum of infections characteristic for the highly immunocompromised patient. The conclude that this pilot study suggests that RS-61443 is effective in refractory kidney allograft rejection. Based on this study, prospectively randomized multi-center trails have been planned and are in progress.