To further characterize the mechanism of impaired growth in children with insulin-dependent diabetes mellitus, we examined the serum components of the insulin-like growth factor (IGF) system in 11 children with new-onset insulin-dependent diabetes mellitus and followed the effect of insulinization on the IGF system longitudinally 1 day, 1 week, and 1 month after starting insulin treatment. Before insulin therapy, serum IGF-I, IGF-II, IGF-binding protein-3 (IGFBP-3), and GH-binding protein (GHBP) levels were significantly decreased, whereas IGFBP-1 and cortisol were significantly increased in diabetic children compared to those in an age-, sex-, and stage of puberty-matched control group. Random serum GH concentrations did not differ significantly. The alterations in the IGF system reversed with insulin therapy in a sequential manner. IGFBP-1 fell rapidly and was comparable to control values within 24 h after insulin treatment. IGF-I rose 1 week after treatment, reaching levels comparable to those in controls and continued to rise through 1 month of treatment. IGF-II, IGFBP-3, and GHBP showed a slower pattern of change, with their levels reaching control values only 1 month after the start of insulin treatment. Improvement in glycemic control, as determined by a change in hemoglobin-A(1c), correlated positively with improvement in IGF-I, IGF-II, IGFBP-3, GHBP, and weight gain after 1 month of insulin therapy.