The secretion of erythropoietin (EPO) and testosterone in response to hypoxia in old (22-25 months), middle (mid)-aged (15-17 months), adult (6-7 months), and young (3 months) male rats was studied. Rats of different ages were bled by cardiac puncture before and subsequent to 8 h exposure to 12% O2. The metabolic clearance rate of EPO was determined by a single-injection method. The effects of orchidectomy and replacement of testosterone propionate on plasma EPO concentrations were also investigated. Analysis of the direct effects of testosterone on EPO release from kidney tissue was carried out in an in vitro study. Both basal and hypoxia-induced EPO levels were lower in old rats than in mid-aged, adult, and young rats (p < .01). Plasma testosterone levels decreased in response to hypoxia in all rats (p < .01 for young, adult, and mid-aged rats, and p < .05 for old rats). The old rats also had lower plasma testosterone levels following hypoxia when compared with other rats (p < .05). The metabolic clearance rate of EPO was not affected by age. Orchidectomy decreased rat plasma EPO concentration (p < .05). This decrease could be restored to intact levels after testosterone propionate replacement. Both 10(-10) M (p < .05) and 10(-9) M (p < .01) testosterone stimulate EPO release from kidney tissue in vitro. Our findings indicate that the basal levels of plasma EPO and testosterone are decreased, and the hypoxia-induced EPO is also diminished with aging in male rats. These data suggest that the mechanism of tolerance to hypoxia and the endocrine function of the kidneys in male rats during the aging process are testosterone-dependent.