Sex steroid priming has been proposed for improving GH response to provocative tests. However, no previous placebo-controlled study of estrogen pretreatment has been performed in short children. We analized the GH response to provocative tests in 31 short children, clinically divided as normal short stature (SS, n=23) chronological age (CA)5 3-15.3, bone age (BA) 3.5-12.9 years and hypopiturtary children (GHD, n=8), CA 5.1- 11.7 years, BA 2.5-8 years. All subjects were prepubertal or in early puberty (Tanner stage ≤ 2). A sequential arginine-clonidine test was performed in two separate occasions, 4 weeks apart. Estradiol (E2 1-2 mg p.o.) or placebo was administered for three days preceeding the GH stimulation test. Results: E2 levels increased from (X±SD)11± 2 to 365±168 pg/ml (p< 0.0001) in SS and from 10 ± 1 to 437± 233 pg/ml (p= 0.003) in GHD. GH maximal responses (GHmax) were 11.0± 9.9 without E2, and 17.6 ±10.7 ng/ml on E2 in short normal children (p= 0.008) and 2.8 ± 2.0 to 3.4 ± 3.2 ng/ml in GH deficient children (ns). The 95% confidence limits for GHmax increased from 3.1-38.6 (without E2) to 6.9-44.7 ng/ml (on E2). With a cut-off of 9 ng/ml no false negative results were observed in the E2 group whereas still 30% failed to respond in the placebo treated group. All patients who failed to respond in the test without E2 priming were older than 10 years. IGF-I levels were 119.0± 41 before and 132.0 ± 46 ng/ml under E2 priming (p < 0.03) in SS and 42.0 ± 64 and 34.0 ± 38 ng/ml (ns) in GHD patients respectively. These findings suggest that E2 priming might improve the discrimination between normal and abnormal GH status in short stature children.