We examined increases in levels of endogenous growth hormone (GH) secretion through exercise, GH-releasing hormone (GHRH), and GH-releasing peptide (GHRP), in patients with demonstrable GH deficiency (GHD) due to either hypothalamic (HT) or pituitary (HP) disease. Eight of 11 HT and four of five HP patients could produce GH levels greater than 5 mU/L, and six of 16 patients could produce GH levels greater than 9 mU/L in this way. Hypoglycemia-stimulated GH and insulin-like growth factor-1 (IGF-1) levels did not predict response. Of 11 HT patients, three failed to respond to any stimulus; one with IGHD, whose peak GH after hypoglycemia was 4.9 mU/L, had normal responses to both GHRH and to exercise. Three who failed to respond to GHRH responded to exercise. Only three patients were tested with GHRH plus GHRP, but in one the GH levels after GHRH, GHRP, and the combination were 5.5, 1.8, and 16.3 mU/L, respectively. In HP patients, the most potent stimulus to GH secretion was the combination of GHRH plus GHRP; GHRP alone had no effect. GHRH alone induced significant GH secretion in four of five patients, indicating the potential for treatment with such peptides.