Age affects time-dependent respiratory responses to episodic hypoxia in male rats, particularly long-term facilitation (LTF), a serotonin-dependent respiratory "memory" [Zabka AG, Behan M, and Mitchell GS, J Physiol (Lond) 531: 509, 2001]. Because age and gender influence serotonergic function, we tested the hypotheses that the short-term hypoxic response (STHR), posthypoxia frequency decline (PHFD) and LTF of phrenic and hypoglossal (XII) motor output change with age and stage of the estrus cycle in female rats. Young (3-4 mo) and middle-aged (13 mo) female Sprague-Dawley rats were anesthetized, paralyzed, vagotomized, and ventilated. STHR was measured during and PHFD after the first of three 5-min episodes of isocapnic hypoxia (arterial P(O)(2) 35-45 Torr). LTF was assessed 60 min postepisodic hypoxia. Phrenic and XII STHR increased with age (P < 0.05). PHFD was unaffected by age or gender. Phrenic LTF increased with age in both estrus and diestrus (P < 0.05), whereas XII LTF increased in middle-aged female rats during diestrus only. Age and gender influence time-dependent hypoxic phrenic and XII responses in a complex manner.