Zinc deficiency is well described in infants on total parenteral nutrition (TPN). Urinary Zn excretion is the major source of Zn loss in the parenterally fed infant; factors causing increased zincuria will predispose the infant to Zn deficiency and affect the recommended Zn intake dosage. Histidine, threonine, and lysine have been shown to bind Zn increasing its renal ultrafilterability. The effect of the infusion of high and low lysine (206 +/- 34 vs 158 +/- 38 mg.kg-1.d-1; means +/- SD), threonine (147 +/- 24 vs 113 +/- 27), and histidine (124 +/- 34 vs 85 +/- 15) on urinary Zn excretion were determined in 23 newborns on TPN who received similar Zn intakes (6.8 +/- 1.4 mumol.kg-1.d-1). After a 72-h adaptation period each infant had urine collected for two 24-h periods. Despite the significant difference in amino acid intakes, mean urinary Zn excretion was identical (1.58 +/- 0.73 vs 1.56 +/- 0.63 mumol.kg-1.d-1). Hyperzincuria, therefore, does not occur when amino acids are infused at rates appropriate for the safety and nutritional maintenance of neonates.