Two subjects with growth hormone (GH) insensitivity were studied using standard methods of examining GH regulation: overnight GH sampling, stimulation of GH secretion with two sequential intravenous injections of GH-releasing hormone (GHRH), and suppression with somatostatin. Subject 1 was a girl, aged 14 years (height, 103 cm; -8.3 SDS for chronological age). Subject 2 was a boy, aged 11.5 years (height, 103.6 cm; -5.9 SDS for chronological age). The overnight pattern of GH secretion was similar in both subjects and appeared pulsatile with three pulses overnight, the major peaks of 203 mU/l and 206 mU/l in subjects 1 and 2 occurring at 00.00 hours and 00.20 hours, respectively. Serum GH levels were detectable throughout and the mean overnight serum GH levels were 65 mU/l and 53 mU/l for subjects 1 and 2 respectively. The pattern of GH response to GHRH stimulation was similar in both subjects, with a large rise in GH after the first injection, to a peak of 512 mU/l and 216 mU/l in subjects 1 and 2 respectively. The response to the second GHRH injection was less than the first, with peaks of 486 mU/l and 150 mU/l. During somatostatin infusion, GH levels fell to 7 mU/l and were undetectable in the two subjects respectively, with a rebound following the cessation of infusion. High resolution computerized tomography (CT) scans of both subjects confirmed normal anatomy of the hypothalamus and pituitary with a small gland at the base of the fossa. In conclusion, GH secretion in GH insensitivity is pulsatile and the pituitary is responsive to exogenous GHRH and somatostatin.(ABSTRACT TRUNCATED AT 250 WORDS)