In children, GH secretion and sensitivity to GH are influenced by developmental changes. It is not clear whether the response to GH in very young children with GH deficiency (GHD) is the same as in older, pre-pubertal children. A cohort of 265 (180 male) children with idiopathic GHD from KIGS (Pfizer International Growth Database), with treatment start at <3 yr (mean age 1.9 yr) (Group I) was compared with a cohort of 509 (331 male) (Group II) with treatment start at 7-8 yr of age (mean age 7.5 yr). The following differences (P < 0.01) were found (given in mean values) between I and II at start of GH: 9% vs. 5% breech delivery, 38% vs. 14% multiple pituitary hormone deficiency (MPHD), 4.2 vs. 5.9 maxGH (ng/ml) to tests, -0.1 vs. -0.8 mid-parental height (MPH) SDS, -3.1 vs. -2.5 height SDS, 0.83 vs. 0.66 GH dose (IU/kg/wk). After the first year of GH, the results were: 13.3 vs. 8.6 height velocity (cm/yr), 1.7 vs. 0.6 height SDS. Using the previously-developed growth prediction models for pre-pubertal children with IGHD >2 yr of age (1), our analysis revealed differences in the indices of responsiveness in prediction models (studentized residuals SDS: 0.7 vs.-0.3), and strikingly higher responsiveness to treatment among the young cohort, but with large scatter. Thus, new prediction models of height velocity (cm/yr) were derived by means of multiple regression analysis for the young cohort, either involving (A) or excluding (B) the GH peak in tests. Model A explained 54% of the total variability with an error SD of 2.1 cm. Height velocity correlated with (parameters in order of importance) age (-), maxGH (-), GH dose (+), WT SDS (+), HT SDS minus MPH SDS (-), and birth weight SDS (+). Model B explained 45% of the total variability with an error SD of 2.3 cm. Height velocity correlated with (parameters in order of importance) age (-), GH dose (+), birth weight SDS (+), HT SDS minus MPH SDS (-), and WT SDS (+). The predictors were qualitatively the same as in the total pre-pubertal model involving all children >2 yr of age, but their quantitative impact in terms of partial contribution and the order of their importance was different for the young cohort. In particular, the partial contribution of the GH dose was higher, suggesting a greater gain in height per GH dose unit in the very young than in older children. However, the rank order of the GH dose in the new models was lower, which suggests a slightly low sensitivity to GH in toddlers, following the phase of severe GH insensitivity during early infancy. The early detection and GH treatment of congenital GHD is advantageous as a cost effective strategy for achieving greater improvement of absolute height and growth velocity.