We treated seven GH-deficient children with 3-hourly 1 microgram/kg sc pulses of GHRH-(1-44) for 6 months and 2 micrograms/kg.pulse for another 6 months. Four patients had a serum GH response to iv GHRH before treatment, and an additional patient responded to iv GHRH after 1 month of pulsatile sc GHRH administration. The mean cumulative growth velocity increased from a pretreatment mean of 2.7 +/- 0.2 (+/- SE) to 8.4 +/- 2.5 and 5.4 +/- 0.7 cm/yr after 2 months and 1 yr of treatment, respectively. Low dose pulsatile GHRH therapy was effective in promoting growth in five of seven children, with height gain ranging from 4.4-7.5 cm at the end of 1 yr's therapy. Only one of the two patients who did not respond to GHRH had an improvement in linear growth when they were subsequently treated with synthetic GH. The other patient, a 16.5-yr-old pubertal girl who had both satisfactory GH and somatomedin-C responses during GHRH therapy, did not respond to either GHRH or, later, synthetic GH. The pretreatment serum GH response to iv GHRH, the serum somatomedin-C concentrations, and the peak serum GH response during sc GHRH therapy were not reliable predictors of clinical response.