The present study was undertaken in order to assess the influence of aging on the endogenous opioid control of gonadotropin and adrenocorticotropin/cortisol secretion in man. For this purpose, the capability of the opioid antagonist naloxone to increase circulating levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and cortisol was tested in male subjects of different ages. Thirty normal men were randomly chosen and divided into 3 groups by age: group I = 22–40 years (n = 10); group II = 41–59 years (n = 10); group III = 62–80 years (n = 10). Since the men of group III showed higher basal serum gonadotropin concentrations than the subjects of group I and group II, we selected from a large population a fourth group of elderly men with normal basal LH and FSH levels: group IV = 61–82 years (n = 7). All subjects were tested for 120 min during the intravenous administration of naloxone (4 mg given in an intravenous bolus at time 0, plus 10 mg infused for 2 h). Control tests with normal saline instead of naloxone were performed in all groups. All subjects had similar blood testosterone and cortisol levels, whereas LH and FSH concentrations were significantly higher in group III than in groups I, II and IV. Naloxone increased plasma cortisol concentrations by 50% in all groups. The cortisol secretory response followed a similar pattern regardless of age. A striking LH and a slight, but significant FSH increase were observed in response to naloxone in groups I and II; in contrast, in the oldest subjects (groups III and IV), naloxone was unable to modify either LH or FSH levels. These data show an impairment of LH and FSH, but not cortisol response, to naloxone in elderly men, suggesting that age induces a selective impairment of endogenous opioid peptides controlling gonadotropin secretion.