Uninephrectomy is associated with increased glomerular filtration rate in both the donated and the remaining contralateral kidney. The long-term effects of ischemic acute renal failure (ARF) following uninephrectomy are unknown. This study examined renal function, histology and proteinuria 52 weeks after an episode of reversible ischemic ARF. Ischemic ARF was induced in uninephrectomised mice by renal pedicle clamping. At 52 weeks inulin clearance (muL/min/g) was 7.2+/-0.2 in sham, 5.0+/-0.1 in uninephrectomy (P<0.01 vs. sham) and 3.9+/-0.1 in uninephrectomy + ischemia (P<0.01 vs. sham, P<0.05 vs. uninephrectomy). Thus, mice subjected to uninephrectomy alone demonstrated compensatory hyperfiltration following reduction in renal mass. This response was prevented by ischemic ARF. At 52 weeks there was no difference in urine protein/creatinine, mean arterial pressure or scores of glomerulosclerosis or interstitial fibrosis. In conclusion, ischemic ARF following uninephrectomy in mice impairs long-term renal function.