In order to determine whether changes in ventilatory control contribute to the observed decrease in arterial partial pressure of carbon dioxide (PaCO(2)) during head up tilt, we assessed ventilatory dynamic sensitivity to changes in PaCO(2) during supine and 70 degrees passive head up tilt. In 24 adult normals, we stimulated the ventilatory control system by switching inspired CO(2) between room air and room air+5% CO(2) in a pseudo random binary sequence. A Box-Jenkins model was used to compute ventilatory response to CO(2). Airflow, CO(2), non-invasive beat by beat blood pressure, ECG and cerebral blood flow velocity (Doppler) were recorded. During tilt, sensitivity of the ventilatory controller to CO(2) disturbance increased (from 0.45 to 0.72 L/min/mm Hg, p<0.005); minute ventilation increased (7.63 to 8.47 L/min, p<0.01), end tidal CO(2) (ETCO(2)), cerebral blood flow velocity (CBF) and baroreflex sensitivity decreased (46.9 to 42.9 mm Hg, p<0.001; 84.9 to 72.9 cm/s, p<0.001; and 17.6 to 5.5 ms/mm Hg, p<0.001). The primary observation from our study was that the sensitivity of ventilatory control system to perturbations in ETCO(2) increased during tilt. Taken together with decrease in mean levels of ETCO(2) and an increase in minute ventilation, these results suggest that during tilt, a change in the regulated level or 'set point' of PaCO(2) may occur.