Aging is associated with an impairment in the GH response to GHRH and to several other stimuli of GH secretion. We evaluated the effect of pyridostigmine (PD) or placebo pretreatment (Protocol A: placebo or 120 mg PD orally at 8 a.m.; Protocol B: placebo or 60 mg PD twice orally at 9 p.m. and 7 a.m.) on GH responsiveness to GHRH (1 micrograms/kg BW bolus i.v. at 9 a.m.) in 15 normal elderly males (65-92 years) and in 14 normal young adults (20-37 years). GH response to GHRH was significantly reduced in elderly subjects compared to young adults (p < 0.05). PD (Protocol A) increased GH release in both elderly and young subjects. In elderly men, PD enhanced GH response to GHRH. The phenomenon was more evident when PD was administered according to Protocol B (p < 0.01). The area under the curve of GH was significantly greater after PD plus GHRH than it was after placebo plus GHRH (p < 0.01). In young adults, PD induced an increase in GH responsiveness to GHRH when administered according to Protocol A (p < 0.05) but not Protocol B. Both GH peak and AUC of GH after PD plus GHRH (Protocols A and B) in elderly subjects were not significantly different from the same parameters found in young subjects after placebo plus GHRH. Our data confirm that pituitary somatotrophin responsiveness to GHRH in man changes with aging. PD restores GH responsiveness to GHRH in elderly subjects. The effect of PD on GH secretion suggests that cholinergic mechanisms may be involved in GH control in normal aging.(ABSTRACT TRUNCATED AT 250 WORDS)