Idiopathic hyperventilation (IH) is a poorly understood condition of sustained hypocapnia and controversial etiology. Although behavioral/emotional factors may contribute, it is uncertain whether chemosensitivity is altered, hyperventilation is maintained during exercise, and the associated breathlessness reflects the hyperventilation. In 39 patients with IH and 23 control subjects, we described ventilatory responses to isocapnic-hypoxia, hyperoxic-hypercapnia, and exercise; breath-hold tolerance; breathlessness; and psychologic status. Patients demonstrated hyperventilation at rest, with hypocapnia (28 +/- 3.8 mm Hg), a normal (slightly alkaline) arterial pH and [H(+)]a, and a significant base excess (-4.5 +/- 2.7 mEq/L), consistent with compensated respiratory alkalosis. Hyperventilation was sustained during exercise, despite hyperoxic-hypercapnic ventilatory responsiveness being normal and isocapnic-hypoxic ventilatory responsiveness being low relative to control (but exceeding control [2.4 +/- 1.0 vs. 1.6 +/- 0.5 L/min/%, p < 0.05] with acute restoration to normocapnia). Hyperventilation was maintained during exercise, at the resting CO(2) "setpoint." Relative to control, the breath-hold tolerance was attenuated, and dyspnea during exercise was significantly greater and not simply ascribable to the high ventilation. These observations suggest that patients with IH have a sustained hyperventilatory and dyspneic drive that, although not attributable to central chemosensitivity, may possibly have peripheral chemoreflex contributions. The nature and etiology of this chronic hyperventilatory drive remain unclear.