Background: Insulin-like growth factor-1 (IGF-1) and IGF-binding protein 3 (IGFBP-3) are used widely for evaluating growth hormone deficiency (GHD). We evaluated the effect of recombinant human growth hormone treatment on serum IGF-1 concentrations in Indian children with GHD over a period of 24 months. Patients and Methods: Patients who presented with short stature were evaluated. The enrolled subjects exhibited a height standard deviation score (SDS) of less than-3 and/ or a height velocity SDS of less than-2 over a 12-month period, and they displayed GH concentrations of less than 10 ng/ml in 2 provocative tests. Patients received a detailed physical examination that included auxology, pubertal staging, and biochemical assays to measure IGF-1 concentration. All patients received GH at a dose of 0.3 mg/kg/week in 7 divided doses subcutaneously daily at night. Patients with multiple pituitary hormone deficiencies received additional substitution therapy. Results: Twenty-five prepubescent children (male: female=14:11) at a mean age of 8.6±2.9 years were enrolled. The height SDS at baseline, 1 year, and 2 years was -5.38±1.4, -4.10±1.4, and -3.6±1.3, respectively (P<0.005), whereas the IGF-1 SDS at baseline, 1 year, and 2 years was -3.40±0.8, -1.74±1.2 and, -1.54±1.7, respectively (P>0.1). No significant difference in height change SDS was detected between children with an IGF-1 SDS in the normal range and children with an IGF-1 SDS of less than -2 at 2 years. Bone age advancement, the occurrence of puberty, and levels of fasting glucose and HbA1C did not change during therapy. Conclusions: Our study on Indian children indicates that changes in serum IGF-1 SDS concentrations may not be a reliable marker for responsiveness to GH therapy.