It has been shown in humans that both alpha 2-adrenoceptor activation by clonidine (CLON) and cholinergic enhancement by pyridostigmine (PD) have a clear-cut stimulatory effect on GH release. As this effect is probably mediated by two different mechanisms, i.e. via increased endogenous GHRH for CLON and via inhibition of endogenous somatostatin for PD, in 8 normal children we studied the effect of both single and combined acute oral administration of CLON (150 micrograms/m2) and PD (60 mg). When administered alone, CLON and PD induced a similar GH increase (peak, mean +/- SE: 14.6 +/- 2.4 vs 14.2 +/- 3.1 ng/ml; area under curve, AUC: 376.9 +/- 57.6 vs 390.0 +/- 74.3 ng/ml/h). Combined administration of CLON and PD had an additive effect on GH release (peak: 27.5 +/- 4.5 ng/ml; AUC: 920.8 +/- 153.3 ng/ml/h; p less than 0.005 vs CLON and PD alone). In conclusion, presented data show that: i) CLON and PD have similar GH-releasing effect in normal children; ii) The additive stimulatory effect on GH release exerted by acute combined administration of CLON and PD agrees with the hypothesized different mechanism of action of these two drugs; iii) A therapeutic association of CLON and PD may be envisaged in the treatment of some children of short stature.