Although the majority of children with isolated GH deficiency have a good growth response to GHRH, the use of this therapeutic agent is limited by its very short half-life. Indeed, we have shown that in mice with GHRH gene ablation (GHRH knock-out- GHRHKO) even twice/day injections of a GHRH analogue are unable to normalize growth. CJC-1295 is a synthetic GHRH analogue that selectively and covalently binds to endogenous albumin after injection thereby extending its half-life and duration of action. We report the effects of CJC-1295 administration in GHRHKO animals. Three groups of 1-week old GHRHKO mice were treated for 5 weeks with 2 µg of CJC-1295 at intervals of 24h, 48h and 72h. Placebo-treated GHRHKO mice and mice heterozygous for the GHRHKO allele served as controls. GHRHKO animals receiving daily doses of CJC-1295 exhibited normal body weight and length. Mice treated every 48h and 72h reached higher body weight and length than placebo-treated animals, without full growth normalization. Femur and tibia length remained normal in animals treated every 24h and 48h. Relative lean mass and subcutaneous fat mass were normal in all treated groups. CJC-1295 caused an increase in total pituitary RNA and GH mRNA suggesting that proliferation of somatotroph cells had occurred, as confirmed by immunohistochemistry images. These findings demonstrate that treatment with once daily administration of CJC-1295 is able to maintain normal body composition and growth in GHRHKO mice. The same dose is less effective when administered every 48h or 72h.