Background: The aim of the study was to investigate and compare components of variance of endogenous markers of glomerular filtration rate (GFR) in healthy dogs and impact on the interpretation of results.Hypothesis: Cystatin C (cysC) in the dog is superior to creatinine (crea) and urea in detecting decreased renal function because of a high index of individuality (IoI).Animals and Method: Variance components of cysC, crea (2 methods: crea E , crea J ), urea, and inorganic phosphate (Pi) in plasma were determined in a longitudinal study over 6 months in 24 healthy dogs (6 German Shorthair Pointers, 18 Beagles). IoI and critical differences (C D ) were calculated, as well as the numbers of measurements necessary to determine the individual's homeostatic set point.Results: Mean concentrations of cysC, crea J , crea E , urea, and Pi (mean 6 SD) were 0.93 6 0.19 mg/L, 0.94 6 0.17 mg/dL, 0.76 6 0.18 mg/dL, 35.34 6 9.08 mg/dL, and 3.74 6 0.68 mg/dL, respectively. The IoI for cysC, crea J , crea E , urea, and Pi were 0.96, 0.89, 0.80, 0.90, and 1.16, respectively. The C D for cysC, crea J , crea E , urea, and Pi were 0.37 mg/L, 0.26 mg/dL, 0.27 mg/dL, 16.94 mg/dL, and 1.45 mg/dL, respectively.Conclusion: In dogs, components of biological variance of cysC and crea are in the same range. Analytical precision requirements were fulfilled by crea both , urea, and Pi. All parameters had an intermediate IoI, which allowed the application of population-based reference limits. The application of the C D for crea or cysC might be useful in detecting a decrease of GFR, when sequential measurements in an individual reveal an increase exceeding the C D but not the upper reference limit.