Persistent pulmonary hypertension of the newborn (PPHN) is a life-threatening disorder of neonates manifested by vasoconstriction of the pulmonary arteries. Recently, the gas nitric oxide (NO) has been used with some success in the management of infants with PPHN. Exogenous administration of NO selectively dilates the pulmonary vascular bed. NO is naturally synthesized in the body from the amino acid L-arginine. Here we report our findings that infants with PPHN are deficient in arginine and achieve normal or elevated plasma arginine concentrations with intravenous hyperalimentation. We prospectively identified and studied 10 infants with PPHN who were not receiving protein or amino acids for at least 24 h and compared their plasma arginine concentrations to 8 control infants without PPHN given similar nutrition. Plasma arginine concentrations were 32 +/- 14 and 52 +/- 20 mumol/l in infants with PPHN and control infants, respectively (p = 0.02). There were no other statistically significant differences in plasma amino acid concentration for any of the 22 other amino acids determined. Infants with PPHN who were subsequently treated with amino acid infusions had plasma arginine concentrations of 115 +/- 48 mumol/l (mean of ten determinations at 86 +/- 27 h after initiation of intravenous amino acids in five PPHN infants).