Acute interstitial nephritis (AIN) is a clinicopathologic entity that is characterized by acute renal failure and renal biopsy findings of interstitial inflammation and tubulitis. There are multiple causes of AIN, the majority of which appear to respond to immunosuppressive therapy. Corticosteroids are the mainstay of treatment for AIN, but many patients are refractory to or intolerant of treatment or are unable to discontinue therapy without clinical relapse. Herein are reported eight cases of steroid-resistant, biopsy-proven AIN that were treated successfully with mycophenolate mofetil (MMF) at one institution. Patients had a mean decline in serum creatinine from 2.3 to 1.6 mg/dl over a mean of 24.3 mo of treatment. Six of the eight patients had a decline in serum creatinine of at least 0.3 mg/dl, and the remaining two patients had stable renal function during the treatment period. At most recent follow-up, five of the eight patients successfully have discontinued treatment with MMF for a mean of 6.4 mo. MMF was well tolerated by all patients. It is concluded that MMF is a useful therapeutic option for steroid-resistant AIN and may be considered as potential first-line therapy in select populations.