We report on GH (0.5 IU or 0.17 mg/kg/week) and GnRH analog (GnRHa, 60 microg/kg, every 4 weeks) therapy in SHOX haploinsufficiency. Case 1 was a 46,XY boy with microdeletion of the Y chromosomal pseudoautosomal region. At 7 years of age, he exhibited short stature (-3.9 SD) with a reduced growth rate (3.8 cm/year), short 4th metacarpals, and mild Madelung deformity. GH therapy resulted in a marked increase in height velocity (10.7 cm/year in the first year). Case 2 was a 46,XX girl with a heterozygous nonsense mutation of SHOX (C674T). At 6 years of age, she presented with short stature (-3.3 SD) with a low height velocity (4.0 cm/year). GH therapy caused a moderate increase in height velocity (6.6 cm/year in the first year and 6.0 cm/year in the second year) before puberty. Because of breast development, she received GnRHa from 9 8/12 years of age. At 10 10/12 years of age, she had mild shortening and borderline curvature of radius. Case 3 was a girl with a 46,X,der(X)t(X;2)(p22.3;p21) karyotype. She was treated with GH from 6 to 14 years of age, and also with GnRHa from 12 to 15 years of age. Her height remained around mean -4 SD, with no discernible alteration of height velocity. At 17 years of age, she had short stature (-4.1 SD), bilateral cubitus valgus, Madelung deformity, and full breast development. The results suggest that GH therapy may have variable statural effects in SHOX haploinsufficiency as in most disorders including Turner syndrome, and that GnRHa therapy after pubertal entry may be insufficient to prevent the development of skeletal lesions such as Madelung deformity.