It has been shown that alpha 2-adrenoreceptor activation induced by clonidine (CLON) increases plasma GH levels in both adults and children. In this study the effects of CLON (150 micrograms/m2, orally) on GH secretion were studied both in the morning (from 0800-1100 h) and at night (from 2300-0200 h) in nine short children previously shown to have normal spontaneous nocturnal GH secretion. In the morning, CLON induced a GH increase higher than placebo [peak (mean +/- SEM), 23.8 +/- 4.3 vs. 3.4 +/- 1.4 micrograms/L; P = 0.0001; area under curve (AUC), 624.4 +/- 62.7 vs. 135.6 +/- 33.3 micrograms/L.h; P less than 0.00001]. In the night, no difference was observed between GH secretion after CLON (peak, 15.4 +/- 3.2 micrograms/L; AUC, 562.2 +/- 57.5 micrograms/L.h) and placebo (peak, 13.1 +/- 4.7 micrograms/L; AUC, 497.2 +/- 83.5 micrograms/L.h). Spontaneous GH secretion was higher during the night than in the morning (P = 0.0001), whereas nocturnal GH secretion overlapped with that in the morning after CLON. The data presented show that alpha 2-adrenoreceptor activation is probably mediated by increased endogenous GHRH release; our results suggest that the endogenous GHRH secretion is maximally stimulated at night.