Nitric oxide (NO) is a potent vasodilator produced by endothelial cells. Endothelin 1 (ET-1), another agent made by endothelial cells, is the most potent vasoconstrictor known to date. Endogenous NO and ET-1 may play a part in the normal physiological pulmonary vascular changes during the postnatal period. However, the changes of NO and ET-1 in healthy neonates have not been defined. We determined serum NO metabolites, i.e., nitrites and nitrates, and plasma ET-1 in 19 healthy neonates at birth (cord blood) and at ages 5 and 30 days. The sums of serum nitrite and nitrate (NOx) levels were 27.5 +/- 12.8, 53.8 +/- 14.2, and 38.3 +/- 13.2 mumol/l at birth, age 5 days, and age 30 days, respectively. The plasma ET-1 concentrations were 3.9 +/- 1.6, 1.1 +/- 0.2, and 1.1 +/- 0.2 x 10(6) mumol/l at birth, age 5 days, and age 30 days, respectively. These changes in healthy neonates suggest the presence of active physiological roles for NO and ET-1 in circulatory adaptation to extra-uterine life.