We previously found that the magnitude of skeletal deficits caused by growth hormone (GH) deficiency varied during different growth periods. To test the hypothesis that the sensitivity to GH is growth period dependent, we treated GH-deficient lit/lit mice with GH (4 mg/kg body wt./day) or vehicle during the prepubertal and pubertal (days 7-34), pubertal (23-34), post-pubertal (42-55) and adult (day 204-217) periods and evaluated GH effects on the musculoskeletal system by DEXA and pQCT. GH treatment during different periods significantly increased total body bone mineral content (BMC), bone mineral density (BMD), bone area and lean body mass [LBM] and decreased % fat compared with vehicle, however, the magnitude of change varied markedly depending on the treatment period. For example, the increase in total body BMD was significantly (P < 0.01) greater when GH was administered between days 42-55 (15%) compared with pubertal (8%) or adult (7.7%) periods while the net loss in % body fat was greatest (-56%) when GH was administered between days 204-216 and least (-27%) when GH was administered between days 7-35. To determine if GH-induced anabolic effects on the musculoskeletal system are maintained after GH withdrawal, we performed DEXA measurements 3-7 weeks after stopping GH treatment. The increases in total body BMC, BMD and LBM, but not the decrease in body fat, were sustained after GH withdrawal. Our findings demonstrate that the sensitivity to GH in target tissues is growth period and tissue type-dependent and that continuous GH-treatment is necessary to maintain body fat loss but not BMD gain during a 3-7 week follow-up.