Gender seems to be an important factor influencing the response to recombinant human growth hormone (rhGH) therapy in GH-deficient adolescents and adults. The results of studies evaluating gender-specific response to rhGH therapy in prepubertal GH-deficient children are divergent. The aim of this study was to determine the effect of gender on the growth and insulin-like growth factor-1 (IGF-1) responses in 75 prepubertal GH-deficient children during the first 2 years of rhGH therapy. There were no baseline gender differences in age, bone age, anthropometrical parameters, and IGF-1 SDS for bone age. After the initiation of rhGH therapy, there were no gender-specific differences concerning the reduction of height deficit. Serum IGF-1 levels were higher in the prepubertal GH-deficient girls than in the age-matched boys, but the difference was not significant when expressed as IGF-1 SDS for bone age. The increase in IGF-1 SDS for bone age was significantly greater in girls versus boys after the first 6 months of therapy, comparable between girls and boys after the first year of therapy, and tended to be higher in boys after the second year of therapy. In conclusion, prepubertal GH-deficient girls and boys do not differ significantly in growth response in the first 2 years of rhGH therapy.