Focal and segmental sclerosed lesions in the glomeruli are found in several pathological entities and more often are found in the corticomedullary junction where renal blood flow and filtration pressure is maximal. Experimental data suggest that hyperfiltration injury results in focal and segmental glomerulosclerosis (FSGS). In keeping with this concept, malignant hypertension is a known cause of nephrotic-range proteinuria and nephrotic syndrome pathalobically represented by FSGS. We report a case of unilateral renal artery stenosis associated with nephrotic syndrome and FSGS in the contralateral kidney only. The kidney with the stenosed renal artery showed normal glomeruli with juxtaglomerular hyperplasia, suggesting that protection from hyperfiltration injury was provided by the presence of high-grade stenosis. Serum creatinine concentration, blood pressure, and proteinuria normalized after aorto-renal bypass surgery. This case shows the importance of hemodynamic factors on the pathogenesis of secondary FSGS and the progression of renal disease.