The efficacy and safety of 1 yr of GH-releasing hormone [GHRH-(1-29)] therapy in GH-deficient children were determined. One hundred and ten previously untreated prepubertal GH-deficient children were treated for up to 1 yr in a multicenter, open label study with 30 micrograms/kg GHRH-(1-29)/day, sc, given at bedtime. Eighty-six of the 110 patients were eligible for efficacy analysis. The main outcome measures, monitored every 3-6 months, were linear growth enhancement (height velocity), bone age progression, and safety measures including clinical chemistry. The mean height velocity for the group increased from 4.1 +/- 0.9 cm/yr at baseline to 8.0 +/- 1.5 and 7.2 +/- 1.3 cm/yr after 6 and 12 months of therapy, respectively. At 6 months, 74% of the children were considered to have a good response to GHRH. The ratio of the change in bone age to height age was not significantly different from unity at 12 months (1.04 +/- 0.58; P = 0.63). No adverse changes in general biochemical or hormonal analyses were noted. No change in fasting glucose concentration or excessive generation of insulin-like growth factor I occurred, and overall GHRH was well tolerated. We conclude that GHRH administered as a once daily dose of 30 micrograms/kg GHRH.(1-29), s.c., was effective in increasing height velocity in GH-deficient children.