GH production rates markedly increase during human puberty, mostly as an amplitude-modulated phenomenon. However, pubertal GH-deficient children have been dosed on a standard per kg body weight basis similarly to prepubertal children. This study was designed to compare the efficacy and safety of conventional (Group I (GI), 0.3 mg/kg.w) vs high dose rhGH Rx (Group II (GII), 0.7 mg/kg.w), in GH-deficient adolescents treated with rhGH for at least 6 mo. 97 children with evidence of GH deficiency (poor linear growth, peak GH to stimuli < 10 μg/L, organic and idiopathic), were recruited. The groups were matched for sex (I:42M, 7F; II: 41M, 7F), age (I: 14.0±1.6 (SD) yrs; II: 13.7±1.6), height SDS (I: -1.4±1.1; II:-1.2±1.1), bone age (BA) (I: 13.2±1.3 yrs; II: 13.1±1.3) and etiology, maximum stimulated GH, previous growth rate and mid-parental target height (Ht). All were in puberty (mean: Tanner Stage 3). Differences from baseline (Δ) were available at 12, 24 and 30 mo. The Δ growth velocity (cm/y) at 12 mo: -0.3±2.5 (I), +1.3±2.8 (II), p=0.005; at 30 mo: -3.8±2.9 (I),-2.0±3.4 (II), p=0.07; Δ Ht (cm): 12 mo: 8.2±2.3 (I), 9.9±2.1 (II), p=0.0004; 30 mo: 18.6±4.7 (I), 21.8±4.8 (II), p=0.02; Δ Bailey-Pinneau predicted Ht (cm): 12 mo: 1.1±4.6 (I), 3.3±4.9 (II), p=0.03; 30 mo: 4.4±5.4 (I), 7.7±6.8 (II), p=0.17. Δ IGF-I: 12 mo: 131±238 μg/L (I), 175±317 (II), p=0.89; 30 mo: 257±255(I), 329±411 (II), p=0.92. No differences in Δ BA were detected between groups at any interval: 30 mo: 2.6±1.2 (I), 2.6±1.1(II), p=0.94. In boys treated ≥2 yrs, the Δ Ht was 4cm greater in the high-dose group. High dose rhGH was well tolerated with no difference in HbA1c or glucose concentrations between groups. Plasma insulin concentrations were higher in GII (p=0.01). In summary: Preliminary analysis shows that as compared to conventional treatment, high dose rhGH Rx in adolescents: 1-increased Ht and Ht SDS scores significantly; 2-did not advance skeletal maturation; 3-appeared to be well tolerated and safe. We conclude: High dose rhGH Rx improves the final adult Ht gain in GH-deficient patients in puberty, without increasing the rate of bone maturation.