Of 16 patients with hyperventilation syndrome (HVS), 11 experienced hypoxemic episodes (defined as PaO2 < or = 60 Torr or SaO2 < or = 90%). To investigate the relationship between hypoxemia in HVS patients and their hypoxic ventilatory response (HVR), we examined 9 of 11 HVS patients who experienced hypoxemic episodes after acute hyperventilation attacks. In order to investigate the genesis of hypoxemia after hyperventilation, we also examined minute ventilation and visual analog scale (VAS) scores representing the sensation of dyspnea at the start and at 70% arterial O2 saturation (SaO2) during HVR in 9 normal subjects under isocapnia and hypocapnia following voluntary hyperventilation (VHV). The HVR of 9 HVS patients who experienced hypoxemic episodes was normal. In 9 normal subjects, minute ventilation and VAS scores representing the sensation of dyspnea at 70% SaO2 during HVR were higher under isocapnia than under hypocapnia following VHV (p < 0.01). VAS scores taken during the HVR immediately following VHV and at 70% SaO2 were not significantly different. HVR and VAS scores representing the sensation of dyspnea were decreased under hypocapnia following VHV. These reductions were thought to be the main factors responsible for the genesis of hypoxemia following acute hyperventilation attacks in HVS patients. We conclude that hypoxemia is an important clinical sign in HVS patients, and it is important to investigate the breathing and chemical drive under hypocapnia, in order to understand the chemical regulation of breathing in HVS patients.