The coadministration of growth hormone (GH) secretagogues can provide insight into the neuroregulation of GH secretion. The GH response to L-dopa (125, 250 and 500 mg orally for body weights 30 kg, respectively), arginine (Arg; 0.5 g/kg infused intravenously over 30 min) and galanin (GAL; 15 µg/kg infused intravenously over 60 min) when administered alone or combined with Pyridostigmine (PD; 60 mg orally), a cholinergic agonist that likely acts via inhibition of endogenous somatostatin secretion, was studied in children with familial short stature. The GH-releasing effect of PD was also evaluated. In 8 children, PD and L-dopa when administered alone induced an equivalent GH rise (area under the response curve, mean ± SEM: 241.4 ± 31.1 vs. 202.9 ± 38.6 µg/l/h) while their coadministration had an additive effect (435.4 ± 41.4 µg/l/h; p < 0.02 vs. PD and L-dopa alone). On the contrary, in other 8 children, PD and Arg induced similar GH increases either when administered alone (394.2 ± 68.5 vs. 405.8 ± 103.9 µg/l/h) or in combination (535.8 ± 97.3 µg/l/h). GH increases almost superimposable were also observed when PD and GAL were administered alone (405.2 ± 72.3 vs. 412.6 ± 94.1 µg/l/h) or in combination (537.9 ± 139.0 µg/l/h) in other 7 children. These data show that the enhancement of the cholinergic activity by PD increases the L-dopa-induced GH release but fails to modify both Arg- and GAL-induced GH release in short children. They may be taken to indicate that a common mechanism, i.e. suppression of endogenous somatostatin secretion, underlies the GH-releasing effect of PD, Arg and GAL, while an extra-somatostatinergic mechanism mediates the