We undertook a 1-year prospective point prevalence study to test the hypothesis that there is an excess of non-diabetic renal disease in native American children; 29.6% (73/247) of the population attending the only regional pediatric nephrology clinic in 1993 were native compared with 8.2% of the Manitoba population in this age group (odds ratio = 4.4, P<0.001). Patients were classified as low risk (normal renal function, no deterioration expected), high risk (normal renal function, deterioration probable), or established chronic renal failure (creatinine clearance chronically low or post renal transplant). Patients were further classified as suffering from congenital renal anomalies, genetic or metabolic disease, or acquired renal disease. Odds ratios were calculated based on data from the Aboriginal Peoples’ Population Survey and Statistics Canada census data. The odds ratios for low-risk renal disease, high-risk renal disease, and chronic renal failure were 3.8, 5.6, and 6.3, respectively (P<0.001 in all categories). The odds ratios for congenital, genetic, or acquired disease were 4.5 (P<0.001), 0.9 (P = ns), and 6.1 (P<0.001), respectively. Native American children in Manitoba demonstrate increased prevalence of serious congenital and acquired renal disease. These children are also more likely to live in medically underserviced communities, long distances from tertiary care centers. This study emphasizes the importance of considering factors other than diabetes mellitus when considering the problem of renal disease in native Americans.