Aim: To determine whether recombinant human insulin-like growth factor-I (rhIGF-I) administration to children with low IGF-I and relatively low insulin-like growth factor binding protein-3 (IGFBP3) serum concentrations would result in hypoglycemia. Methods: Eighteen children age 11-19 y with serum levels of IGF-I < -2 SDS and IGFBP3 <0 SDS were randomly assigned to receive rhIGF-I at 80 μg/kg body weight daily (n = 6), 40 μg/kg twice daily (n = 6), or 80 μg/kg twice daily (n = 6). After a 10-d dose escalation and 15 d of treatment at the specified dosage, a 25-h pharmacokinetic/ pharmacodynamic profile was obtained, which included 22 blood glucose measurements. Regular meals and snacks were provided. Results: No signs or symptoms of hypoglycemia were noted throughout the study. There were no differences in mean blood glucose concentrations among the three dosage groups. The lowest glucose value recorded, 3.44 mmol/l, was 15 min after a morning injection of 80 μg/kg IGF-I, and promptly rose. Although subjects were selected on the basis of low concentrations of IGF-I to represent proposed candidates for rhIGF-I therapy, the mean and range of SDS for height were not different from those of previously studied normal Ecuadorian controls. Conclusion: In normal individuals with low serum concentrations of IGF-I and relatively low concentrations of IGFBP3, the administration of therapeutic doses of rhIGF-I, while maintaining reasonable food intake, does not result in hypoglycemia.