We studied properties of saliva and of dental plaque which affect the caries process in an effort to understand the low prevalence of caries in patients with chronic renal failure. Plaque pH, before and following carbohydrate exposure, saliva pH, and saliva composition were evaluated in children and adolescents with chronic renal failure (n=10) and successful renal transplantation (n=11), and in two comparison groups of healthy children with few caries (n=15) and numerous caries (n=15). Salivary urea nitrogen concentration was elevated in all subjects with elevated serum urea nitrogen concentration. Chronic renal failure subjects had significantly higher salivary urea nitrogen concentration than transplanted subjects. Plaque pH correlated directly with salivary urea nitrogen concentration and was significantly more alkaline in chronic renal failure than transplant or comparison groups. Salivary urea nitrogen concentration accounted for the majority of variability in plaque pH; salivary pH and salivary phosphorous contributed negligibly. Absolute pH drop following carbohydrate exposure did not differ among groups, but because baseline plaque pH was elevated for chronic renal failure subjects, minimum pH did not attain cariogenic levels. Our data support the hypothesis that the relative paucity of caries in patients with chronic renal failure results from alteration of plaque by metabolic end products of urea metabolism. Our data further suggest that transplanted patients whose renal function is normal may be at increased risk of caries, especially if enamel hypoplasia is present and oral hygiene is poor.