The effect of general anesthesia on control of breathing was studied by CO2 rebreathing and occlusion pressure measurements in six normal human subjects under methoxyflurane anesthesia. CO2 was found to increase the amplitude of the occlusion pressure wave without changing its shape, so that CO2 responses in terms of the occlusion pressure developed 100 ms after the onset of inspiration (Po/0.1) gave results equivalent to the responses in terms of Po/1.o or any other parameter of the pressure wave. Methoxyflurane depressed the ventilatory response to CO2 but not the occlusion pressure response, implying that the most important action of the anesthetic was to increase the effective elastance of the respiratory system rather than to depress the respiratory centers. The elastance was further increased by CO2, and this mechanical change had the effect of shifting the "apneic threshold" extrapolated from the ventilatory response curve to a lower PAco2. Frequency of breathing, inspiratory and expiratory times were not altered by CO2 in anesthetized subjects.