Continuous insulin infusion (CII) was used to increase intravenous glucose tolerance in 10 extremely premature (26.2 +/- 0.04 weeks, means +/- SEM) very low birth weight (819 +/- 53 g) hyperglycemic infants. CII was continued for 3-36 days. Over the first 72 h of insulin administration the mean amount of glucose tolerated rose from 0.35 +/- 0.06 to 0.67 +/- 0.06 g/kg/h and caloric intake derived from intravenous glucose increased from 29 to 56 kcal/kg/day. Insulin doses required to maintain normoglycemia ranged from 0.005-0.052 U/kg/h initially to 0.002-0.086 U/kg/h after 72 h of CII. Plasma insulin levels were significantly higher during insulin infusion. The low insulin doses required to maintain normoglycemia were consistent with a state of relative insulin deficiency, rather than insulin resistance. Mean plasma insulin/glucose ratios were significantly higher in normoglycemic versus hyperglycemic infants (0.40 +/- 0.08 vs. 0.14 +/- 0.05). Less than 1% of all blood glucose estimations were less than 25 mg/dl. Seventy-eight percent were within the normal range (greater than 45, less than 130 mg/dl). The rate of weight gain increased during CII in 8 of the 10 infants. CII may be useful in extremely premature, very-low-birth-weight infants in whom glucose intolerance persists despite conservative treatment, and either severely limits caloric intake, or results in life-threatening hyperglycemia.