The role of opioidergic system in controlling gonadotropin secretion in elderly men still remains uncertain. In the present study, we attempted to examine the opioidergic inhibitory tone imposed on GnRH release mechanism in elderly men by monitoring the plasma gonadotropin response to the opiate receptor antagonist naloxone hydrochloride. Six normal young men and 10 elderly men with no endocrinological diseases volunteered for the present study. In young men, plasma LH showed a biphasic increase in response to naloxone and plasma LH level during naloxone treatment was significantly higher than the mean of prenaloxone control levels. In contrast, plasma LH in elderly men was not affected by naloxone. The ratio of the peak plasma LH response during naloxone treatment to the mean pre treatment LH level (plasma peak/basal LH ratio) declined with the advance of age (r = -0.74, P < 0.005) and also correlated significantly with plasma free testosterone level (r = 0.45, P < 0.05). These data suggest (1) that the hypothalamic opioidergic tone is reduced in elderly men and (2) that the primary testicular insufficiency with the advance of age may play a major role in the decline of the hypothalamic opioidergic tone in elderly men.