Hypertension is a likely consequence of chronic lead exposure in man, especially in association with reduced renal function and in high risk populations. Numerous studies have demonstrated that oxidative stress plays an important role in the pathogenesis of experimental lead-induced hypertension and we have shown recently that tubulointerstitial immune cell infiltration is a feature of chronic low dose lead exposure. Since oxidative stress, renal inflammation and angiotensin activity are closely linked characteristics in experimental models of hypertension, we decided to investigate if lead-induced hypertension would be ameliorated by suppressing renal inflammation with the immunosuppressive drug mycophenolate mofetil (MMF). We studied rats exposed for 14 weeks to lead acetate (100 ppm in the drinking water) that, in addition, received either MMF, 20mg/kg/day by gastric gavage (Pb.MMF group, n=12) or vehicle (Pb group, n=12). Control rats received MMF alone (n=5) or neither lead nor MMF (n=6). All rats were sacrificed at the end of the experiment. Low-dose lead exposure resulted in mild to moderate tubular cell damage, and a progressive increment if blood pressure, oxidative stress, interstitial accumulation of lymphocytes and macrophages, NF-B activation and increased renal angiotensin II level. The administration of MMF suppressed the tubulointerstitial accumulation of lymphocytes and macrophages and prevented the hypertension, oxidative stress, NF-B activation and reduced the heightened renal angiotensin content associated with chronic lead exposure. We conclude that interstitial inflammation plays an important role in lead-induced hypertension