Withdrawal of a somatostatin infusion (SSIW) is followed by a rebound rise of GH in both animals and normal adult men, a phe- nomenon likely mediated by endogenous GHRH function. In the present study, we have evaluated the GH response to SSIW in a group of 28 prepubertal children (18 boys and 10 girls; aged 3.7-11.1 yr). Six children had GH deficiency (GHD; GH responses to pyridostigmine (PD)1GHRH and to clonidine ,20 and ,7 mg/L, respectively), 4 children had GH neurosecretory dysfunction (GHND; GH responses to PD1GHRH and to clonidine $20 and .7 mg/L, respectively; mean integrated nighttime GH concentrations ,3 mg/L), and 18 children were short normal children (normal controls (NC)). All children re- ceived a constant infusion of SS at the dose of 3 mg/Kgzh for 90 min. SSIW elicited a clear-cut GH rise in NC children (13.7 6 1.0 mg/L), but not in GH-deficient children, regardless of the underlying etiology (GHD, 1.6 6 0.4 mg/L; GHND, 2.4 6 0.3 mg/L). The GH response to SSIW was similar between GHD and GHND children. There was no overlapping of the maximum SSIW-stimulated GH peaks between NC and GHD or GHND children. In conclusion, we have demonstrated that SSIW elicits a significant GH rise in NC children, but not in GH-deficient children, regardless of the underlying etiology (GHD or GHND). This resulted in complete discrimination of NC from GHD or GHND children. Were these present findings confirmed on a larger number of children, SSIW, because of its testing efficaciousness and safety, procedural simplic- ity, and economy holds promise of being a useful diagnostic tool for GH-dependent growth disorders. (J Clin Endocrinol Metab 84: 4426 - 4430, 1999)