The reduced activity of the growth hormone (GH)-insulin-like growth factor I (IGF-I) axis in aging may contribute to changes in body composition. As this GH insufficiency is due to hypothalamic pathogenesis, the availability of GH-releasing peptides (GHRPs), such as GHRP-6 (His-D-Trp-Ala-Trp-D-Phe-Lys-NH2) which is active even after oral administration, might be useful to restore it. The aim of our study was to verify the effectiveness of oral administration of GHRP-6 in normal elderly subjects and to investigate whether its GH-releasing activity is maintained or vanishes after short-term oral treatment. Seven normal elderly women (aged 65-82 years) were studied. The effect of oral administration of 300 micrograms/kg GHRP-6 on GH secretion was investigated before and after 4 days of treatment with the hexapeptide given twice daily. The GH response to the maximal effective dose of GHRH (1 microgram/kg i.v.) also was studied. Before treatment, oral administration of 300 micrograms/kg GHRP-6 elicited a clear GH rise (peak 10.7 +/- 3.3 micrograms/l; AUC 353.1 +/- 90.6 micrograms.l-1.h-1), which was significantly higher (p < 0.01) than that induced by intravenous GHRH (peak 5.1 +/- 1.5 micrograms/l; AUC 106.5 +/- 43.9 micrograms.l-1.h-1). After 4 days of treatment with GHRP-6, the GH response to the hexapeptide was maintained, with a trend towards an increase (peak 16.8 +/- 2.9 micrograms/l; AUC 499.8 +/- 107.2 micrograms.l-1.h-1). The IGF-I levels were not increased significantly after treatment (77.1 +/- 8.4 vs 84.1 +/- 12.2 micrograms/l).(ABSTRACT TRUNCATED AT 250 WORDS)