Severity of renal injury and recovery offunction in acute renal failure (ARF) are strongly related not only to the magnitude and nature of ARF insult but also to numerous factors in the host which govern renal susceptibility to the insult and repair of renal lesion. Prior ARF aflords resistance to a rechallenge with the same or different ARF insult. The mechanism for this acquired resistance to ARF have not been well established, but suggested mechanisms include (a) increased resistance of regenerated tubular epithelial cells to a rechallenge, (b) glomenrlar refractoriness to vasoactive substances, (c) failure of damaged kidney to concentrate the toxic substance, (d) enhanced antioxidant enzyme activity in glomeruli, and (e) increased Na+-K+-A Pase activity in regenerated tubular epithelial cells. Controversy still exists regarding roles of these factors in the resktance to renal failure. Functional and morphologic recovery of postischemic kidney is enhanced by antecedent unilateral nephrectomy but delayed in the presence of the contralateral kidney. The mechanisms for the effect of uninephrectomy remain unsettled. Recent studies suggest contributions of changes in preglomeruhr vascular resktance; alterations in the environment which follow ischemia to all functioning wcretory renal tissues; and altered production and release of vasoactive substances such as angiotensin, endothelin, thromboxane, and atrial natriuretic peptide.