Sex hormones modulate plasticity in the central nervous system, including respiratory long-term facilitation (LTF), a form of serotonin-dependent respiratory plasticity induced by intermittent hypoxia. Since gonadectomy (GDX) attenuates LTF in male rats (Zabka et al., 2005), we tested the hypotheses that: 1) testosterone replenishment restores LTF in gonadectomized male rats, and 2) that the conversion of testosterone to estradiol (under the influence of aromatase) is required for these effects. Intact and sham operated male F344 rats were compared to gonadectomized rats implanted with Silastic® tubing containing testosterone (T), T plus an aromatase inhibitor (ADT), or 5 alpha-dihydrotestosterone (DHT), a form of testosterone not converted to estradiol. Seven days post-surgery, LTF was studied in anesthetized, paralyzed and ventilated rats while monitoring integrated phrenic and hypoglossal (XII) motor output. LTF was elicited by 3, 5-min hypoxic episodes (PaO2=35- 45 mmHg). Although significant phrenic and XII LTF were observed in all rat groups, GDX reduced both phrenic and XII LTF, an effect reversed by T. In contrast, LTF was not restored in T + ADT or DHT-treated gonadectomized rats. We conclude that the conversion of testosterone to estradiol modulates phrenic and XII LTF in male F344 rats.