The factors that initiate chronic renal failure in patients with hypertension, diabetes mellitus, and chronic glomerular disease are largely unknown. The likely genetic contribution to ESRD, particularly in African Americans, suggests that linkage analysis may be useful to evaluate the role of candidate genes in the pathogenesis of chronic renal failure. The renin-angiotensin-aldosterone (RAA) axis has been intensively evaluated for its contribution to cardiovascular disease and nephropathy. This study tested for linkage between candidate genes in the RAA axis and chronic renal failure, using 85 African-American sibling pairs (from 65 families) concordant for ESRD. Angiotensinogen was selected because of the putative link between it and mild to moderate essential hypertension and nephrosclerosis; angiotensin-converting enzyme because of its possible contribution to diabetic nephropathy; and renin, the angiotensin II receptor, and kallikrein because of their roles in hypertension and renal perfusion. These candidate loci did not demonstrate linkage to either diabetic or nondiabetic renal disease in this study's collection of sibling pairs. These results suggest that polymorphisms at these RAA axis loci do not make major contributions to the pathogenesis of renal disease in African Americans.