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Normotensive male Wistar rats are susceptible to the development of glomerulosclerosis, a process which can be accelerated by partial renal ablation, while normotensive male Wistar Kyoto (WKy) rats are resistant to glomerulosclerosis. Long-term treatment with angiotensin-I-converting enzyme inhibitors prevents the development of glomerulosclerosis. We studied the acute renal vascular response to bolus injections of captopril (1, 3, and 10 mg/kg). Mean arterial blood pressure (MAP) was significantly less in Wistar rats compared to WKy and not influenced by unilateral nephrectomy. Renal vascular resistance (RVR) and the filtration fraction (FF) were significantly greater in sham and unilateral nephrectomy Wistar rats as compared to WKy. Captopril significantly reduced the RVR in all four groups, but at comparable doses, RVR remained greater in the Wistar sham and Wistar rats following unilateral nephrectomy compared to sham and uninephrectomized WKy respectively. Captopril reduced FF in Wistar rats only. These data indicate an enhanced level of activity of the renal renin-angiotensin system in glomerulosclerosis-susceptible Wistar rats compared to glomerulosclerosis-resistant WKy rats, suggesting that vascular reactivity involving the renin-angiotensin system is an important determinant of the genetically determined differences in susceptibility to glomerulosclerosis in these two rats strains. The strain-dependent difference in RVR at the highest dose of captopril indicates that additional, possibly structural features may play a role in the difference in susceptibility to glomerulosclerosis.