Unilateral warm renal ischemia of 90 min duration was induced in rats and the contralateral normal kidney was removed either immediately or after 1, 2, 4 or 14 d. Contralateral nephrectomy at 2, 4, 14 d increased survival and modified the functional and morphological events of the recovery period. Optimal recovery was obtained by 4 d delay. When contralateral nephrectomy was delayed by 14 d, scarring of the ischemic kidney was more severe suggesting that regeneration of damaged nephrons was impaired when renal homeostasis was sustained by the contralateral kidney. Such biphasic and inverse effects of normal kidney tissue are likely to be important determinants of the natural history of severe unilateral renal damage.