Intravenous infusions of the synthetic hexapeptide GH-releasing peptide (His-DTrp-Ala-Trp-DPhe-Lys-NH2; GHRP) specifically stimulate GH release in man. To determine whether orally administered GHRP stimulates GH secretion, 10 normal men received oral doses of placebo, 30, 100, and 300 micrograms/kg GHRP, and an iv injection of 1.0 micrograms/kg GHRP at weekly intervals in a single blind, randomized design. Serum GH concentrations were measured in blood samples obtained at 5-min intervals for 1 h (0700-0800 h) before and 4 h (0800-1200 h) after each dose. Mean (+/- SE) peak GH concentrations were 4.0 +/- 1.5, 5.2 +/- 1.6, 9.2 +/- 3.3, 18 +/- 3.7, and 26 +/- 5.6 micrograms/L for placebo; 30, 100, and 300 micrograms/kg oral GHRP; and 1 micrograms/kg iv GHRP, respectively; mean 4-h (0800-1200 h) integrated GH concentrations were 312 +/- 109, 406 +/- 159, 698 +/- 284, 1264 +/- 303, and 1443 +/- 298 min.micrograms/L, respectively. To analyze changes in the pulsatile pattern and amount of GH secretion after the administration of GHRP, a waveform-independent deconvolution method was used to estimate GH secretion rates. Variable increases in GH secretion after placebo and GHRP treatments were observed. Despite this variability, weighted least squares linear regression revealed that increasing doses of oral GHRP progressively stimulated GH secretion (P less than 0.005); similar relationships were observed for the peak GH concentration and 4-h integrated GH concentrations. The GH responses to oral GHRP (300 micrograms/kg) and iv GHRP (1 microgram/kg) were significantly greater than that to placebo (P less than 0.05) and were comparable in magnitude. Pairwise comparisons revealed that increases in GH concentrations and secretion rates after the 30 and 100 micrograms/kg oral doses of GHRP were not significantly different from those after placebo. The increase in GH secretion after GHRP treatment was accounted for entirely by an increase in the amplitude of GH secretory events, as no significant increase in the number of GH secretory pulses was observed. The onset and duration of action of GHRP were analyzed by a proportional hazards general linear regression model. Intravenous GHRP had a more rapid onset of action than all doses of oral GHRP (P less than 0.02). Increasing doses of oral GHRP resulted in earlier GH responses (P = 0.006). However, the duration of the GH response was similar for iv GHRP and all doses of oral GHRP, averaging 120-150 min.(ABSTRACT TRUNCATED AT 400 WORDS)