Synthetic, amidated, 44 amino acid GH-releasing hormone ( GRH -44) was administered iv at a dose of 5 micrograms/kg to 20 patients with severe GH deficiency (GHD), 6 children and adolescents with partial GHD, and 6 non-GH deficient ( NGHD ) children and adolescents. The 17 patients with severe GHD that responded to GRH -44 had lower peak concentrations of plasma GH than the NGHD individuals (5.0 +/- 1.2 (SEM) vs. 27.2 +/- 3.5 ng/ml; P less than 0.0001). The children and adolescents with severe GHD tended to have higher peak GH responses to GRH -44 than the GHD adults (6.9 +/- 1.7 vs. 2.4 +/- 0.3 ng/ml) although the difference was not significant. The peak GH concentration was attained earlier in the GHD children and adolescents than in the GHD adults (28 +/- 4.7 vs. 69.3 +/- 13 min, P less than 0.004). There was a negative correlation between chronological age and peak plasma GH response to GRH in the children and adolescents with severe GHD (r = -0.758, P less than 0.02). Children and adolescents with partial GHD had a higher mean peak concentration of plasma GH (13. 1 +/- 1.8 ng/ml) than the children, adolescents, and adults with severe GHD (P less than 0.04), but one lower than the NGHD children and adolescents (P less than 0.05). In both severe and partial GHD the GH response to GRH was greater than that elicited by standard pharmacological tests. Serum somatomedin-C did not increase after a single pulse of GRH -44 in the 12 GHD patients studied. PRL increased minimally 30 min after 5 micrograms/kg iv GRH -44 in patients with multiple hypothalamic-pituitary hormone deficiencies but not in patients with isolated GHD or in NGHD individuals. The GH responses to GRH suggest that the majority of patients with isolated GHD as well as those with multiple hypothalamic-pituitary hormone deficiencies have deficiency of hypothalamic GRH . Lack of a GH response to a single pulse of GRH does not exclude GRH deficiency as priming of the somatotrope with multiple pulses of GRH may be necessary to rule out a hypothalamic defect in the nonresponders. The results of this study support the potential usefulness of GRH or its analogs in the diagnosis and treatment of selected patients with disorders of GH secretion.