Renal handling of magnesium (Mg) has not been comprehensively studied in the newborn period due to the difficulty, until recently, of measuring the diffusible fraction of plasma Mg (UfMg). In the present study this methodology was used to assess Mg homeostasis in 84 newborn infants of different postconceptional age (26-42 weeks), weight (720-4,830 g) and postnatal age (1-72 days). Very premature infants (postconceptional age less than 35 weeks) had significantly higher values of plasma Mg than mature newborn infants. Plasma Mg related inversely to postconceptional age, weight, plasma total protein and plasma calcium, and directly to plasma potassium. Stepwise multiple regression analysis revealed that postconceptional age was the unique factor contributing to variations in plasma Mg. Plasma values of UfMg were the same in preterm as in term infants but, when expressed as a fraction of total plasma Mg (UfMg/Mg), they were significantly lower in very preterm infants. Fractional excretion of Mg and the ratio of urine Mg to urine creatinine did not vary as a function of postconceptional age. These results indicate that plasma UfMg is kept constant at different gestational ages despite variations in total plasma Mg; furthermore, no functional immaturity is present for renal tubular reabsorption of Mg, even in very low birth weight infants.