Plasma creatinine levels are elevated in the first postnatal days, and the highest plasma creatinine values are observed in the most premature infants. These high plasma creatinine levels remain "elevated" beyond the period in which the high plasma creatinine levels can be explained by maternal transfer of creatinine. To better define the renal handling of creatinine by the immature kidney, creatinine and inulin clearances were simultaneously measured in two groups of neonatal and one group of adult anesthetized, ventilated rabbits. In the adult animals the ratio of the creatinine and inulin clearance was as expected more than one (1.21), indicating an overestimation of the true GFR due to tubular secretion of creatinine. The creatinine and inulin clearance ratio in the first group of newborn animals, who received an exogenous creatinine infusion to achieve plasma creatinine levels comparable to those in the adult animals (84.1 +/- 1.0 mumol/L; 0.95 +/- 0.01 mg/dL), was 0.84. When in the second group of neonatal animals the plasma creatinine level was artificially doubled to 155.0 +/- 3.9 mumol/L (1.33 +/- 0.17 mg/dL), no significant difference between both clearance values was found (ratio: 0.96). These data show that in the newborn rabbit creatinine is reabsorbed along the tubule, an observation that can best be explained by the back-leak of creatinine across leaky immature tubules.