The aim of our study was to investigate the effects of aging on the growth hormone (GH) response to growth hormone-releasing hormone (GHRH) alone and in combination with either the neuropeptide galanin or the acetyl-cholinesterase inhibitor pyridostigmine (PD) in normal subjects. In protocol 1 (GHRH/galanin), 9 old healthy volunteers, ranging in age from 68 to 97 years, and 6 young subjects, ranging in age from 25 to 31 years, received: (a) human GHRH (1-29)NH2, 100 mug in 1 ml saline, as an intravenous bolus, and (b) porcine galanin, 500 mug in 100 ml saline, as an intravenous infusion from - 10 to 30 min combined with GHRH, 100 mug i.v. at time 0. In protocol 2 (GHRH/PD), 14 old healthy volunteers, ranging in age from 65 to 91 years, and 11 young subjects, ranging in age from 19 to 34 years, received: (a) GHRH (1-29)NH2, 100 mug in 1 ml saline, as an intravenous bolus, and (b) PD, 120 mg administered per os 60 min before GHRH, 100 mug as an intravenous bolus. Blood samples for GH were drawn at - 75, - 60 (time of PD administration), - 45, - 30, - 15, - 10 (time of beginning of galanin infusion), 0 (time of GHRH injection), 15, 30, 45, 60, 90, and 120 min. The GH response to GHRH was significantly ( < 0.05) enhanced either by galanin or PD pretreatment both in young and old subjects. However, the GH response to GHRH alone or combined with either galanin or PD was significantly greater in the young subjects as compared to the old subjects. Our data suggest that alterations in the hypothalamic control of GH secretion may only in part be responsible for the blunted GH response to GHRH in the aged.