A microcomputer feedback system has been developed which adjusts the inspired minute volume of a ventilator based on the patient's end-tidal CO2 concentration. The feedback controlled ventilator was evaluated in 6 dogs (18-20 kg). Arterial PCO2 was monitored continuously while end-tidal CO2 concentration was controlled by the micro-computer system and the following perturbations introduced: [1] NaHCO3 was infused IV, [2] a pulmonary artery was occluded, [3] one lumen of a double lumen endobronchial tube was occluded, and [4] an air embolism was given. The end-tidal PCO2 controller kept PaCO2 within 1.2 mm Hg of the desired value when CO2 production increased by as much as 44%. Changing the ventilation/perfusion ratios caused differences as large as 22 mm Hg between the arterial and end-tidal PCO2 and the controller was not effective in keeping PaCO2 at the desired level. Closed loop control of ventilation based on end-tidal PCO2 measurements successfully compensated for increases in CO2 production keeping PaCO2 constant. The controller did not, however, keep PaCO2 at the desired level when significant changes occurred in the distribution of blood flow to ventilation.