We hypothesized that the ventilatory threshold and sensitivity to carbon dioxide in the presence of hypoxia and hyperoxia during wakefulness would be increased following testosterone administration in premenopausal women. Additionally, we hypothesized that the sensitivity to carbon dioxide increases following episodic hypoxia and that this increase is enhanced after testosterone administration. Eleven women completed four modified carbon dioxide rebreathing trials before and after episodic hypoxia. Two rebreathing trials before and after episodic hypoxia were completed with oxygen levels sustained at 150 Torr, the remaining trials were repeated while oxygen was maintained at 50 Torr. The protocol was completed following 8-10 days of treatment with testosterone or placebo skin patches. Resting minute ventilation was greater following treatment with testosterone compared with placebo (testosterone 11.38 +/- 0.43 vs. placebo 10.07 +/- 0.36 l/min; P < 0.01). This increase was accompanied by an increase in the ventilatory sensitivity to carbon dioxide in the presence of sustained hyperoxia (VSco(2)(hyperoxia)) compared with placebo (3.6 +/- 0.5 vs. 2.9 +/- 0.3; P < 0.03). No change in the ventilatory sensitivity to carbon dioxide in the presence of sustained hypoxia (VSco(2 hypoxia)) following treatment with testosterone was observed. However, the VSco(2 hypoxia) was increased after episodic hypoxia. This increase was similar following treatment with placebo or testosterone patches. We conclude that treatment with testosterone leads to increases in the VSco(2)(hyperoxia), indicative of increased central chemoreflex responsiveness. We also conclude that exposure to episodic hypoxia enhances the VSco(2 hypoxia), but that this enhancement is unaffected by treatment with testosterone.