Aging is associated with decreased GH and insulin-like growth factor-I (IGF-I) levels and lean body mass, and increased body fat. Recombinant human GH treatment of old men partially reverses body composition changes. Administration of GH-releasing hormone (GHRH) to GH-deficient children and young adults increases GH and IGF-I levels while preserving physiological GH release. We investigated whether GHRH injections restore GH and IGF-I levels in old men to the levels in young men. Healthy young (n = 9; 26.2 +/- 4.1 yr; mean +/- SD) and old (n = 10; 68.0 +/- 6.2 yr) nonobese men underwent baseline blood sampling for measurements of IGF-I and 24-h profiles of GH release, followed by iv bolus GHRH stimulation tests. Old men then took, randomly, both low (0.5 mg) and high (1 mg) dose GHRH-(1-29) sc injections twice daily for 14 days, with an intervening 14-day nontreatment period. The study protocol was repeated on day 14 of each treatment. At baseline, the mean peak duration of spontaneous GH release (P less than 0.005) and IGF-I levels (P less than 0.0001) were lower in the old men. GHRH treatment evoked dose-related increases in all parameters, with significant differences (vs. old basal values) in mean 24-h GH (P less than 0.001), area under peaks (P less than 0.001), peak amplitude (P less than 0.05), and IGF-I (P less than 0.005) only at the high dose. After high dose treatment, there were no significant differences in these parameters between age groups. Peak and integrated responses to iv GHRH stimulation tests did not differ between young and old men either before or during GHRH treatment. Baseline serum levels of both testosterone (P less than 0.01) and phosphate (P less than 0.05) were lower in the older men. Phosphate levels increased (P less than 0.05) during GHRH treatment. GHRH treatment did not affect fasting glucose, urinary C-peptide, blood pressure, or chemistry and hematology profiles. Thus, short term sc administration of GHRH to healthy old men reverses age-related decreases in GH and IGF-I, suggesting that prolonged treatment could improve age-related alterations in body composition.