The urinary excretion and proximal tubular reabsorption of .beta.-2-microglobulin was studied in 17 healthy newborn infants in relation to gestational [GA] and post-natal age. The effect of IRDS [idiopathic respiratory distress syndrome] and non-conjugated hyperbilirubinemia on the tubular reabsorption of the protein was evaluated in 10 IRDS infants and 14 infants with non-conjugated hyperbilirubinemia. The urinary excretion of .beta.-2-microglobulin was determined under standardized conditions. When GFR [glomerular filtration rate] was determined, the single injection clearance method was used. The filtered load of .beta.-2-microglobulin increased with increasing GA. This was due to a rise in plasma .beta.-2-microglobulin concentration as well as to a rise in the GFR. Although the smallest filtered load was recorded in infants with a mean GA of 32.4 wk, these infants had a lower fractional reabsorption of the protein (88%) than infants with a mean GA of 35.0 wk or more (98%). In infants with a GA of 35 wk or more, a glomerulo-tubular balance for .beta.-2-microglobulin was established. In these infants the filtered load of .beta.-2-microglobulin increased rapidly during the 1st days of life. This was paralleled by an increase in the reabsorptive capacity for the protein. In infants with IRDS and in infants with non-conjugated hyperbilirubinemia the fractional reabsorption of .beta.-2-microglobulin was lower than in control infants of a corresponding gestational and postnatal age. In the neonatal period, the proximal tubular transporting capacity is more vulnerable than the glomerular filtration rate in states of hypoxia and hyperbilirubinemia.