Bolus doses of GH-releasing hormone (GHRH), 1 µg/kg i.v., were given to two groups of adult patients with growth hormone deficiency (GHD): 9 with Hand-Schüller-Christian disease (HSCD, presumed hypothalamic GHD) and 9 with idiopathic GHD (IGHD, etiology unknown). Six patients in each group were then given further GHRH doses daily for 5 days, and the GH responses to GHRH were measured over 3 h on day 1 and day 5. Plasma levels of insulin-like growth factor-1 (IGF-1) were measured twice daily on days 1 and 5 during GHRH treatment. All patients with HSCD had measurable GH responses to the first dose of GHRH, with a mean peak response of 6.4 ± 2.1 ng/ml (X ± SE). Only 5 of 9 patients with IGHD had GH responses above the detection limits of the assay; their mean peak response, 1.3 ± 0.2 ng/ml, was significantly lower than the GH responses of the HSCD patients (p < 0.05). Responses in both groups of patients were lower than those previously observed in normal adult men (35 ± 8 ng/ml; p < 0.01). Five days of daily stimulation with GHRH significantly (p < 0.01) increased the GH response in both groups of patients. The rise was greater in patients with HSCD than with IGHD (HSCD, 5.1 ± 2.5 ng/ml on day 1, vs. 12.0 ± 6.8 ng/ml on day 5; IGHD, 1.4 ± 0.3 ng/ml vs. 2.9 ± 0.6 ng/ml). Plasma IGF-I levels rose significantly over the 5 days in both groups; this rise was also greater in the HSCD patients (HSCD, 0.37 ± 0.06 vs. 0.64 ± 0.1 U/ml; IGHD, 0.38 ± 0.12 vs. 0.45 ± 0.12 U/ml, p < 0.05). Responses in this group of HSCD patients confirm the expectation that patients with ‘pure’ hypothalamic GHD should have GH responses to GHRH, and that diminished initial responses reflect somatotroph atrophy which can be reversed with repeated GHRH stimulation.