In man the GH response to GHRH is highly variable and some normal subjects may be completely unresponsive to the neuropeptide. On the other hand, the potentiation of cholinergic activity by pyridostigmine (PD), a cholinesterase inhibitor, increases the GH response to GHRH, probably by inhibiting somatostatin release. The aim of this study was to assess the existence of intraindividual variability in the GH response to GHRH and verify the effects of PD treatment on inter- and intraindividual variability. Twenty normal adults (17 M and 3 F) and 10 normal prepubertal children (9 M and 1 F) underwent 2-5 administrations of 1 micrograms/kg GHRH on different days. Seven adults and all children also underwent 1-5 other tests in which GHRH was preceded (60 min before) by oral PD (120 mg in adults and 60 mg in children). The GH responses to GHRH were highly variable, not only within subjects but also in the same subject on different occasions (peak range; adults: 0.4-49.0 ng/ml; children: 2.4-50.0 ng/ml). PD always markedly increased the GH response to GHRH, even unmasking this response in 3 adults and 4 children hyporesponsive to the neuropeptide alone. However, the variability in the GH response was still present (adults: 27.2-108.5 ng/ml; children: 25.0-144.0 ng/ml), though reduced (adults: p = 0.0005; children: p = 0.0204). These data indicate that: i. A great inter- and intraindividual variability in the GH response to GHRH is present.(ABSTRACT TRUNCATED AT 250 WORDS)