Endocrine changes occur during the normal aging process. These include alterations in GH, TSH and, to a lesser extent, PRL secretion. Pyrodistigmine (PD) increases basal GH secretion in a widely variable manner and partially reverses the blunted GH response to GHRH found in elderly subjects. The aims of this study were to verify the finding of a paradoxical GH response to TRH (200 micrograms iv) and to evaluate the effect of priming with PD (120 mg orally) on basal and TRH-stimulated GH, TSH and PRL secretion in 7 euthyroid subjects (aged 75-96 years). Hormonal responses after control saline and PD were also evaluated. PD did not modify TSH or PRL responses to TRH. A slight increase in GH secretion was observed after PD. A clear-cut increase in GH levels after TRH was found in 4 out of 7 subjects. TRH-induced GH secretion was significantly increased by pretreatment with PD. Functional abnormalities in the neuroendocrine control of GH secretion in aging could explain, at least in part, the appearance of GH release after TRH. Cholinergic neurotransmission, which is thought to be stimulated by PD administration, seems to be involved in the non-specific GH release after TRH administration in elderly subjects.