A computerized system that uses feedback of end-tidal CO2 fraction (FETCO2) to adjust minute volume of a ventilator has been developed and tested. The effectiveness and robustness of the controller were evaluated in five anesthetized dogs. The controller responded to step-changes in the set-point for FETCO2 by adjusting minute volume so that the FETCO2 settled to the new set-point in less than 60 sec with less than 20% overshoot. The system exhibited suitable dynamic response to step-changes in set-point with loop gains as large as two times and as small as one-half the optimal value. The breath-to-breath variation in FETCO2 values during prolonged periods of closed-loop controlled ventilation was smaller than the variation during periods of constant minute volume ventilation in three of five experiments. The controller generally maintained FETCO2 within +/- 0.1 vol% of the set-point. A disturbance to the controlled system was produced by releasing an occlusion of a branch of the pulmonary artery. The controller always responded to this disturbance in a stable manner, returning the FETCO2 to its desired value within 30 sec. Accurate control of arterial partial pressure of CO2(PaCO2) will require modifications enabling the system to determine the relationship between FETCO2 and PaCO2.