Multiple, stimulus-specific cellular mechanisms give rise to phrenic long-term facilitation (pLTF), a well-studied form of respiratory neuroplasticity. We recently demonstrated that circulating sex hormones are critical for induction of pLTF following moderate acute intermittent hypoxia (mAIH; 35-45mmHG PaO2) in adult female rats; mAIH-induced pLTF is not expressed during estrous cycle stages with low circulating 17β-estradiol (the most neuroactive form of estrogen) or following removal of the ovaries, the primary source of circulating sex hormones. Castrated male rats also do not express mAIH-induced pLTF supporting a link between circulating sex hormones and pLTF expression in males as well. More severe AIH protocols (sAIH; 25-35mmHg PaO2) induce pLTF through a unique set of cellular pathways. However, all studies of sAIH-induced pLTF to date have been completed in young-adult, gonadally-intact male rats. Our primary Aims for these studies were two-fold: 1) determine if sAIH-induced pLTF was expressed in female rats across stages of the estrous cycle; and 2) determine if removal of the gonads (ovaries or testicles) influenced expression of sAIH-induced pLTF. We hypothesized that sAIH-induced pLTF would be expressed in females regardless of estrous cycle stage, and that sAIH-induced pLTF would be expressed in both females and males following removal of the gonads. Young adult (12-13 weeks) female and male Sprague-Dawely rats were used for each study. In study 1, pLTF was quantified in female rats on the morning of estrus (low circulating 17β-estradiol) or proestrus (high circulating 17β-estradiol) based on examination of vaginal cell characteristics in vaginal smears using light microscopy. In study 2, ovariectomy or castration was completed at least 7 days prior to pLTF assessments. Contrary to our hypothesis, preliminary results suggest that sAIH-induced pLTF may be significantly influenced by circulating sex hormones. Though female rats exhibited sAIH-induced plasticity across estrous cycle stages, the magnitude of pLTF was associated with circulating estradiol levels. Additionally, removal of the gonads abolished the expression of sAIH-induced pLTF in both female and male rats, suggesting a direct influence of sex hormones on sAIH mechanisms to pLTF. These data provide further evidence that sex hormones may play a critical role in expression of AIH-induced respiratory neuroplasticity.