In preterm neonates, functional limits of pulmonary and/or renal regulation processes and the considerable acid load of common formulas predispose to a great risk for the development of latent metabolic acidosis, characterized by e.g. impaired mineralization and reduced growth. Furthermore, in a prospective study in very low birth weight-infants, latent metabolic acidosis was assumed to contribute to the development of nephrocalcinosis. To obtain fundamental data of acidbase regulation in preterm infants under different diets, we investigated 48 preterm infants fed their own mother`s milk (28 native human milk, 20 enriched with fortifier) and 34 patients on formula (23 on a standard batch, 11 on a modified batch with reduced acid load). Irrespective of the diet, we could not find notable differences between individual data of acid-base status in blood samples. In contrast, dietary acid-base intake was accurately reflected in the urine, pointing to effective individual compensation of alimentary acid-load by renal base saving mechanisms. Thus, in preterm infants, nutritional acid-base challenges can be judged earlier and more safely by urinary than by blood acid-base analysis A physiologically based and empirically adjusted calculation model allows to estimate the impact of mineral and protein content of a formula on the urinary ionogram and thus on the average renal net acid excretion in a regularly fed and growing preterm infant. The algorithm of this proposed calculation model could prove to be a useful tool in the design of new formulas with adaequate base supply for preterm infants.