Atherosclerotic renovascular disease (ARVD) is commonly associated with renal failure. It is now recognized that intrarenal damage, (ischaemic or atherosclerotic nephropathy) is a major contributor to the renal impairment in these patients. In this study the impact of histological changes upon renal functional outcome was investigated in patients with atherosclerotic nephropathy. The Hope Hospital renal biopsy database (1985-1998) was interrogated for patients with histology compatible with atherosclerotic nephropathy. Case-note review enabled the assessment of several clinical parameters and outcomes, including change in creatinine clearance per year (DeltaCrCl (ml/min/year)), blood pressure control, dialysis need, and death. Renal parenchymal damage was analysed by morphometric analysis (of interstitial fibrosis and glomerulosclerosis) and a semi-quantitative chronic damage score (score 0-3 (normal-severe) for each of glomerulosclerosis, interstitial fibrosis, tubular atrophy, and arteriolar hyalinosis; maximum=12). Patients were stratified into two groups who had either deteriorating (group 1) or stable (group 2) renal function during follow-up. Twenty-five patients (age 64.7+/-10.5, range 43-83 years; 17 male, eight female) were identified. Sixteen patients had undergone angiography; two had significant (>50%) renal artery stenosis. Mean follow-up was 25.6+/-14.8 (range 5-50) months. Group 1 patients had DeltaCrCl -7.4+/-6.8 ml/min/year, n=14 and group 2 patients had DeltaCrCl 4.8+/-7.0 ml/min/year, n=11. Four patients in group 1 developed end-stage renal disease and five patients died (three in group 1 and two in group 2). At study entry, group 1 patients had worse renal function (CrCl 27.6+/-17.6 vs 36.0+/-33.9, NS), greater proteinuria (1.2 vs 0.5 g/24 h, NS), and higher systolic blood pressure (167.1+/-30.8 mmHg vs 150.6+/-37.8, NS) compared with group 2 patients. Group 1 patients showed more glomerulosclerosis (51.6 vs 24.9%, P:<0.01), greater proportional interstitial volume (44.9 vs 33.9%, P:<0.02), and higher overall chronic damage score (P:<0.05) than those in group 2. There was a significant correlation between renal functional outcome and chronic damage score, glomerulosclerosis and proportional interstitial volume for the entire patient cohort. In patients with atherosclerotic nephropathy the severity of histopathological damage is an important determinant and predictor of renal functional outcome.