Urinary endothelin-1-like immunoreactivity (ET-1-LI) excretion was determined in 31 neonates, six sick infants with renal dysfunction secondary to neonatal asphyxia and 25 healthy infants, during the first week of life to clarify its evolutional change and the origin of the urinary ET-1-LI in the newborn period. Urinary ET-1-LI concentrations in the healthy infants maintained the same level during the first week of life (n = 35, 36 +/- 22 pg/mg creatinine, mean +/- SD). There was no difference in urinary ET-1-LI excretion in infants between 30 and 41 weeks of gestation. Urinary ET-1-LI concentrations in the sick infants were significantly elevated through the first week of life when compared with those of healthy infants. Fractional excretion of sodium and endothelin clearance were more elevated in the sick infants than in the healthy infants. A good correlation was observed between urinary ET-1-LI concentrations and urinary N-acetyl-beta-D-glucosaminidase index (r = 0.72, p < 0.01). These results suggest that the origin of urinary endothelin-1 may be the renal tissue and that ET-1 may be a nonspecific marker of renal injury in neonates.