This investigation was designed to determine if suppression of testosterone alters the ventilatory response to carbon dioxide in the presence of high and low levels of oxygen. Eleven healthy male subjects completed a series of rebreathing trials during wakefulness, before and after treatment with a long-acting gonadotropin-releasing hormone agonist. Five subjects also completed studies during non-rapid eye movement (NREM) sleep. During wakefulness, subjects initially hyperventilated to reduce the partial pressure of carbon dioxide (PET,CO2) below 25 Torr. Subjects then rebreathed from a bag containing a normocapnic (42 Torr), low (50 Torr) or high oxygen (140 Torr) gas mixture. During each trial PET,CO2 increased while oxygen was maintained at a constant level. The threshold of the ventilatory response to carbon dioxide was considered to be the point at which minute ventilation began to rise in a linear fashion as PET,CO2 increased. The slope of the ventilatory response above the threshold was used as a measure of sensitivity to carbon dioxide. During NREM sleep, hypocapnia was induced via nasal mechanical ventilation. Several trials were completed until the cessation of mechanical ventilation resulted in a central apnoea which demarcated the threshold of the ventilatory response to carbon dioxide. In response to treatment with leuprolide acetate, the threshold measured in wakefulness decreased during carbon dioxide rebreathing in the presence of low (41.05 ± 0.77 versus 39.40 ± 0.83 Torr; P= 0.01) and high (46.32 ± 0.56 versus 44.78 ± 0.83 Torr; P= 0.01) oxygen levels. An increase in sensitivity (4.82 ± 0.61 versus 7.17 ± 1.20 l min−1 Torr−1; P= 0.02) was also observed during rebreathing in the presence of high but not low oxygen levels. The increase in sensitivity was accompanied by an increase in carbon dioxide production. The findings observed during NREM sleep were similar to those observed during wakefulness, since the PET,CO2 that demarcated the threshold was decreased after leuprolide treatment (42.1 ± 0.6 versus 39.6 ± 0.6 Torr; P= 0.002). Additionally, the decrease in PET,CO2 required to induce an apnoea was greater after treatment with leuprolide (2.56 ± 0.25 versus 4.06 ± 0.29 Torr; P= 0.004). We conclude that suppression of testosterone decreases the threshold of the ventilatory response to carbon dioxide during both wakefulness and sleep.