The urinary excretion and proximal tubular reabsorption of beta-2-microglobulin was studied in 17 healthy newborn infants in relation to gestational and post-natal age. The effect of IRDS 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 was determined, the single injection clearance method was used. The filtered load of beta-2-microglobulin was found to increase with increasing gestational age. 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 weeks, these infants had a lower fractional reabsorption of the protein (88%) than infants with a mean GA of 35.0 weeks or more (98%). In infants with a GA of 35 weeks or more a glomerulo-tubular balance for beta-2-microglobulin apparently was established. In these infants the filtered load of beta-2-microglobulin increased rapidly during the first 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. This indicates, that in the neonatal period, the proximal tubular transporting capacity is more vulnerable than the glomerular filtration rate in states of hypoxia and hyperbilirubinemia.