We have evaluated the effects of the combined administration of Galanin (Gal) plus growth hormone-releasing hormone (GHRH) and of pyridostigmine (PD), a cholinergic agonist, plus Gal on GH secretion in 15 children (12 males and three females, age 7.7-14.5 y) with short stature. Children were subdivided into two groups. In group 1 (n = 7) Gal (15 micrograms/kg h i.v.) plus GHRH (1 microgram/kg i.v.) administration induced a higher GH rise (peak = 73.1 +/- 10.2 ng/mL, mean +/- SD; area under the curve (AUC) = 531.9 +/- 78.7 ng.min.mL-1) than did GHRH alone (peak = 38.9 +/- 26.5 ng/mL, p less than 0.05; AUC = 256.9 +/- 165.6 ng/mL/min-1, p less than 0.005). Gal had a synergistic effect on the GHRH-induced GH response because the GHRH plus Gal AUC response was significantly higher (p less than 0.01) than the sum of the areas of response to GHRH and Gal alone. In group 2 (n = 8) PD administration (60 mg/kg p.o.) had no significant effects on the Gal-induced GH secretion (peak = 14.9 +/- 8.8 and 16.0 +/- 9.8 ng/mL after Gal and PD + Gal, respectively; AUC = 91.2 +/- 52.1 and 125.2 +/- 83.6 ng.mL.min-1 after Gal and PD + Gal, respectively). Our results confirm the ability of Gal to stimulate GH secretion in children, and strengthen the view that its mechanism of action involves modulation of endogenous somatostatin release.