Recent studies in adults have shown that cholinergic enhancement by pyridostigmine (PD) has a stimulatory effect on growth hormone (GH) response to GH-releasing hormone (GHRH). PD probably reduces somatostatin release from the hypothalamus by increasing the central cholinergic tone. The aim of this study was to evaluate the effect of PD (120 mg orally) or placebo pretreatment on GH responsiveness to GHRH (1 micrograms/kg b.w. i.v.) or placebo in 10 normal elderly males (68-92 years). PD induced a significant increase in GH secretion (GH peak 7.3 +/- 1.8 micrograms/L, mean +/- SEM) over the basal value (0.9 +/- 0.2 micrograms/L; P less than 0.01) and enhanced GH response to GHRH (peak after GHRH: 17.0 +/- 3.8 micrograms/L; after PD plus GHRH: 42.6 +/- 12.2 micrograms/L; P less than 0.05). There was a significant difference in the secretory areas of GH among tests (P less than 0.05). The secretory area was greater after PD plus GHRH (2722 +/- 801 micrograms/L/120 min) than after GHRH (1185 +/- 206 micrograms/L 120 min; P less than 0.01). The effect of PD on GH secretion suggests that cholinergic mechanisms may be involved in GH control in normal aging. During the life-span cholinergic neurons and/or the somatostatin pathways could exert a differential effect on GH control.