Pathologic changes in nonneoplastic renal parenchyma of nephrectomy specimens for renal tumors and the significance of these changes with regard to the outcome of contralateral kidney function have not been studied previously. We examined the nonneoplastic renal parenchymal changes in 110 consecutive tumor nephrectomy specimens, and we correlated our findings with patients' clinical information. The material was examined for the presence of any glomerular, tubulointerstitial, or vascular pathology. In our analysis, only about 10% of cases had unremarkable renal parenchyma and vasculature. A further 28% of cases had unremarkable parenchyma, but some degree of vascular sclerosis was noted. The remaining cases (>60%) had evident pathologic abnormalities, most commonly related to vascular disease or diabetes mellitus. Regardless of the type of renal cancer they have, the majority of our cases can be placed in one of three principal groups: 1) unremarkable kidney parenchyma, with or without vascular sclerosis (38%); 2) parenchymal scarring and marked vascular changes, including cases of atheroembolic disease, and chronic thrombotic microangiopathy (28%); and 3) changes related to diabetes mellitus, such as glomerular hypertrophy, mesangial expansion, and diffuse glomerulosclerosis (24%). Follow-up data on serum creatinine 6 months postoperatively were available in a third of our patients. Patients with severe histopathologic findings (parenchymal scarring with >20% global glomerulosclerosis and advanced diffuse diabetic glomerulosclerosis) showed a significant change in serum creatinine from the preoperative period to 6 months after radical nephrectomy (P=0.001), indicative of progressive worsening of renal function; this change is significantly greater than that seen in patients with unremarkable renal parenchyma (P=0.01). We conclude that adequate examination of nonneoplastic renal parenchyma is an important tool in recognizing patients at risk for progressive renal disease after nephrectomy and could be an essential step in providing early preventive and treatment measures and better medical care of patients undergoing nephrectomy for neoplastic processes.