To determine the duration of respiratory arrest needed to attain a PaCO2 level high enough to provide maximal stimulation of respiration, we evaluated changes in PaCO2, PaO2 and apH during periods of apnea lasting as long as 10 minutes in 10 apparently brain-dead subjects. Before apnea, mean PaCO2 was 33 mm Hg. In seven subjects who did not breathe for 10 minutes, the mean rate of rise of PaCO2 was 3.2 mm Hg per minute. PaCO2 at 4 minutes was 50 mm Hg and at 10 minutes was 67 mm Hg. Three subjects breathed, two after less than 2 minutes of apnea, when PaCO2 was 47 and 54 mm Hg, and one after 4.5 minutes, when PaCO2 was 47 mm Hg. These data indicate: (1) that the threshold for respiratory stimulation may approach a PaCO2 of 60 mm Hg in patients with brain damage; (2) that the rate of increase in PaCO2 is such that, even in a normocapnic subject after 3 minutes of apnea, the PaCO2 may not be sufficiently high to stimulate respiration; and (3) if a patient is hypocapnic prior to the onset of apnea, PaCO2 may not reach 60 mm Hg even after 15 minutes. To confirm absolute apnea, then, blood gas monitoring is necessary for verification of normocapnia prior to the beginning of apnea. In the absence of blood gas determinations, no fixed period of apnea, sufficient in all cases to establish absolute apnea, can be ascertained.