We had previously shown that the hypothalamo-neurohypophyseal vasopressin secreting system is suppressed in aged rats. In the present study, using aged (26 months) male Fischer 344 (F344) rats, we showed that in contrast to vasopressin, oxytocin plasma concentration and hypothalamic content were unaltered in comparison with young (2–3 months) rats; however, based on data from our past and current studies, the neurohypophyseal concentrations of both hormones were found to be decreased in aged rats. We also compared the effect of aging on the oxytocin and vasopressin in secretory functions. Superfusion technique was employed to examine oxytocin and vasopressin release from isolated neural lobes of young (2–3 months) and old (26 months) male F344 and young (2–3 months), middle-aged (12 months) and old (30 months) Sprague-Dawley (SD) rats. Aging affected basal release of oxytocin and vasopressin in a differential manner. Expressed per gland, basal release of oxytocin increased in aged rats of both strains; whereas vasopressin release decreased in SD, and did not change in F344, old rats. The vasopressin responses to electrical stimulation, 56 mM K+ and initial traumatic release were decreased in aged rats; whereas oxytocin responses were either unaltered or decreased much less. All age-related changes were more pronounced in SD than in F344 rats. Thus, while the aging process is associated with a significant impairment in the vasopressin secretory function, the oxytocin secretory function is much less affected by that process. Significant strain differences were observed in the effects of aging on oxytocin and vasopressin re