The present study determined the effect of immune suppression with mycophenolate mofetil (MMF) on sodium-sensitive hypertension following recovery from ischemia reperfusion (I/R)-induced acute renal failure. Male Sprague-Dawley rats fed 0.4% NaCl chow were subjected to 40 min bilateral I/R or control sham surgery. After 35 days of recovery, when plasma creatinine levels had returned to normal, the rats were switched to 4.0% NaCl chow for 28 days and administered vehicle or MMF (20 mg.kg(-1).day(-1) ip). High-salt mean arterial pressure was significantly higher in I/R rats (144 +/- 16 mmHg) compared with vehicle-treated sham rats (122 +/- 2 mmHg). Treatment of I/R rats with MMF during the period of high salt intake prevented the salt-induced increase in arterial pressure (114 +/- 3 mmHg). Conscious creatinine clearance was lower in I/R rats (0.27 +/- 0.07 ml.min(-1).100 g body wt(-1)) compared with vehicle-treated sham rats (0.58 +/- 0.04 ml.min(-1).100 g body wt(-1)); MMF treatment prevented the decrease in creatinine clearance in I/R rats (0.64 +/- 0.07 ml.min(-1).100 g body wt(-1)). I/R injury also significantly increased glomerular tissue damage and increased the presence of ED-1 positive (macrophages) and S100A4 positive cells (fibroblasts) in the renal interstitium. The I/R rats treated with MMF exhibited a significant reduction in infiltrating macrophages and fibroblasts and decreased histological damage. The present data indicate that infiltrating immune cells mediate or participate in the development of sodium-sensitive hypertension and renal damage in rats apparently recovered from renal I/R injury.