Background: Carbon dioxide elimination (Vco(2)) at steady state corresponds to the metabolic rate. A change in tidal ventilation will lead to a transient response in Vco(2) if other determinants of Vco(2) are constant. This principle may be applied in the critical care unit to reset ventilators. Objective: To define and characterize the transient response of Vco(2) to a well-defined change in ventilation. Methods: Forty-four patients in stable condition receiving volume-controlled mechanical ventilation had trend recordings of ventilator pressures, now, volumes, Vco(2), and end-tidal CO2 (ETco(2)) for 20 min. At time t(0), the minute ventilation was either increased (n = 22) or decreased (n = 22) by 10% after which these parameters were monitored over 30 min. Blood gas values were measured 5 and 20 min after the change in ventilation and the dead space fractions were computed using the single breath-CO2 test. Data analysis: The first ten breaths (till t(1)) after a change in ventilation were excluded. The time constant (tau) of the relative change in Vco(2) (Delta Vco(2)) was calculated by fitting exponential regressions to Delta Vco(2) for periods up to 20 min after t(1). Results: The Delta Vco(2) at t(1) was proportional to the relative change in tidal volume (Delta V Tau). The proportionality decreased gradually during 20 min. The proportionality of the relative change in ETco(2) (Delta ETco(2)) or PaCO2 (Delta PaCO2) with Delta V Tau was minimal at t(1) and increased during the 30 min. tau increased progressively when calculated over longer periods (p < 0.001), tau was similar in the groups with increased and decreased ventilation up to 5 min, after which it was longer in the group with decreased ventilation (p < 0.05). The Delta PaCO2 after 20 min correlated best with Delta Vco(2) at t(1) (r = -0.8) and with Delta ETco(2) at the end of 20 min (r = 0.8). Conclusions: Noninvasively monitored Vco(2) provides an instantaneous indication of the change in alveolar ventilation in well-sedated, mechanically ventilated patients in stable condition without significant cardiopulmonary disease.