Twenty severely GH-deficient prepubertal children aged 10.7 +/- 2.1 yr (mean +/- SD) and with a height SD of -4.92 +/- 1.02 were treated with sc injections of GHRH 1-44 (10 micrograms/kg BW) for 6 months either daily (11 patients) or 3 times/week (nine patients). An acute iv GHRH test (2 micrograms/kg BW) was performed before and after 2 and 6 months of treatment. Mean (+/- SD) peak GH responses to these tests were 2.92 +/- 3.01, 4.57 +/- 4.91, and 7.56 +/- 8.14 micrograms/L, respectively (P less than 0.05, pretreatment vs. 6 months). The mean growth velocity (GV) during treatment was only 2.99 +/- 1.67 cm/yr and only two patients increased their GV by more than 2 cm/yr. A correlation was found between GV during treatment and the peak serum GH response to GHRH acute test before treatment (r = 0.68, P less than 0.005) as well as between GH response to the acute test and patient's bone age (r = -0.46, P less than 0.05). The results indicate that in some severely GHD patients with no response to GHRH even after a 2-month priming period, 6 months of treatment with GHRH can evoke pituitary responsiveness. We speculate that the duration of the GHRH deficiency and its severity plays a role in the ability of somatotrophs to respond to this stimulus.