The transient presence of infiltrated leukocytes in the kidney during acute renal failure as well as the location of these cells within the renal interstitium suggest their association with tubular injury and/or regeneration. To date, however, neither a positive nor a negative contribution of these cells to the pathophysiology of this disease could be unambiguously demonstrated. Ill-defined methods for identifying interstitial leukocytes have added to the controversy concerning the role of inflammatory cells in renal regeneration. The current literature survey presents a qualitative description of the renal interstitial accumulation of leukocytes as observed in some acute renal failure models, with special attention to those displaying acute tubular necrosis of particular nephron subsegments. We conclude that lethal or sublethal injury to renal tubular epithelial cells following toxic or ischemic insults leads to the manifestation of an interstitial mononuclear cell infiltrate. Whereas macrophages and T lymphocytes almost invariably take part, the former being the dominant cell population with respect to both magnitude and presence over time, polymorphonuclear cells seem to be significantly increased only in the case of pyelonephritis. Infiltrating cells have often been regarded rather harmful to the tissue, mainly due to the quite well understood injuring capacity of the latter. On the other hand, we speculate mononuclear leukocytes through their potential of producing different cytokines and growth factors (FGF, TGF-α, EGF-like, IL-2, etc.) might well play an initiating and mediating role in renal regeneration after acute tubular necrosis. Therefore, the role of infiltrating leukocytes in the injury/regeneration process during acute renal failure remains highly controversial and should be further elucidated.