ABSTRACT: Lifespan in rodents is prolonged by caloric restriction (CR) and by mutations affecting the somatotropic axis. It is not known if CR can alter the age-associated decline in growth hormone (GH), insulin-like growth factor (IGF)-1 and GH secretion. To evaluate the effect of CR on GH secretory dynamics; forty-three young (36.8 +/- 1.0 years), overweight (BMI 27.8 +/- 0.7) men (n = 20) and women (n = 23) were randomized into four groups; control = 100% of energy requirements; CR = 25% caloric restriction; CR + EX = 12.5% CR + 12.5% increase in energy expenditure by structured exercise; LCD = low calorie diet until 15% weight reduction followed by weight maintenance. At baseline and after 6 months, body composition (DXA), abdominal visceral fat (CT) 11 h GH secretion (blood sampling every 10 min for 11 h; 21:00-08:00 hours) and deconvolution analysis were measured. After 6 months, weight (control: -1 +/- 1%, CR: -10 +/- 1%, CR + EX: -10 +/- 1%, LCD: -14 +/- 1%), fat mass (control: -2 +/- 3%, CR: -24 +/- 3%, CR + EX: -25 +/- 3%, LCD: -31 +/- 2%) and visceral fat (control: -2 +/- 4%, CR: -28 +/- 4%, CR + EX: -27 +/- 3%, LCD: -36 +/- 2%) were significantly (P < 0.001) reduced in the three intervention groups compared to control. Mean 11 h GH concentrations were not changed in CR or control but increased in CR + EX (P < 0.0001) and LCD (P < 0.0001) because of increased secretory burst mass (CR + EX: 34 +/- 13%, LCD: 27 +/- 22%, P < 0.05) and amplitude (CR + EX: 34 +/- 14%, LCD: 30 +/- 20%, P < 0.05) but not to changes in secretory burst frequency or GH half-life. Fasting ghrelin was significantly increased from baseline in all three intervention groups; however, total IGF-1 concentrations were increased only in CR + EX (10 +/- 7%, P < 0.05) and LCD (19 +/- 4%, P < 0.001). A 25% CR diet for 6 months does not change GH, GH secretion or IGF-1 in nonobese men and women.