Due to the abrupt increase in 2,3-diphosphoglycerate (2,3-DPG) concentration in the newborn lamb, which begins soon after birth, this interval in development was considered an excellent period to test the hypothesis that glucose perfusions could inhibit 2,3-DPG synthesis. Ten newborn lambs were divided into two groups and perfused either with glucose (15 mg/kg/min) or physiologic saline (45% NaCl) for 10 days. Blood gases, electrolytes, glycemia, O2pressure at 50% Hb saturation, and 2,3-DPG levels were compared in the two groups. Glucose levels remained significantly elevated during the first 3 days in the glucose perfused group. The O2pressure at 50% Hb saturation increased in both groups but was significantly lower in the glucose perfused group when determined on day 5 and 8. The postnatal increase in 2,3-DPG was significantly diminished in the glucose infused lambs, which suggests that glucose perfusion has an inhibiting effect on erythrocyte 2,3-DPG synthesis. (Pediatr Res24: 470–472, 1988)