The combined growth hormone-releasing hormone and growth hormone-releasing peptide-6 (GHRH + GHRP-6) test is most potent in evaluating GH secretion. To assess its capability in children with GH deficiency and low spontaneous GH secretion (GH neurosecretory dysfunction). 35 children with GH <10 microg/l after levo-dopa/clonidine (GHD), 15 with normal provocative tests but abnormal 24-hour spontaneous GH secretion (GHND), and 20 controls (C) were given 1 microg/kg of GHRH and GHRP-6 i.v. and GH (microg/l) was measured at -15, 0, 5, 10, 15, 30, 45 and 60 min. Six were nonresponders to the combined test, with significantly lower peak GH 20.7 (7.8-31.8) than C and the rest of the patients (responders). Peak GH was similar between prepubertal (PP) controls 167 +/- 88, GHD 202 +/- 110 and GHND 155 +/- 83. Pubertal (P) controls had higher peak GH 328 +/- 149 than P-GHD 203 +/- 105 and P-GHND 186 +/- 105. While P-C had higher peak GH than PP-C, PP and P children had similar responses within the GHD and GHND groups. The GHRH + GHRP-6 test detects children with severe GH insufficiency. Patients with GHD respond similarly to those with GHND, indicating a possible hypothalamic GH neuroregulatory dysfunction in GHD. Responders to the combined test may be eligible for treatment with a synthetic GH secretagogue.