More than 80% of children with growth hormone deficiency (GHD) respond with a rise in growth hormone levels when given 1 microgram/kg body weight of growth hormone-releasing hormone (GHRH) in an i.v. bolus. We conducted a study to determine whether the failure of the remaining 20% to respond to GHRH is due to a pituitary deficiency or a secondary effect associated with chronically understimulated somatotrophs. We administered GHRH to "prime" 16 short-statured children (> 2 SD) presenting delayed growth (< 4 cm/year), who had not responded initially when given a single dose of GHRH. Priming consisted of administering GHRH (1-29) NH2 (5 micrograms/kg body weight, s.c.) for six consecutive days. Plasma GH response was studied again after an i.v. injection of 1 microgram/kg body weight of GHRH (1-29) NH2 on the seventh morning. On the basis of these results we were able to separate our patients into two groups: a) responders to priming (n = 8), whose GH responses to pharmacological and acute GHRH tests were < 10 ng/ml, with a 12-hour sleep secretion < 3 ng/ml/min. Priming increased the plasma GH response to acute GHRH in all the children in this group (6.0 +/- 2.1 ng/ml to 18.0 +/- 5.4 ng/ml; p < 0.001); b) non-responders to priming (n = 8), whose GH responses to pharmacological and acute GHRH tests were also < 10 ng/ml, with 12-hour sleep secretion < 3 ng/ml/min, but in whom priming with GH did not increase the plasma GH response (5.5 +/- 2.8 ng/ml to 6.2 +/- 2.9 ng/ml; p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)