Currently available estimates of the PaCO2 rate of rise in resting humans with resting lung volume were gathered during general anesthesia. The PaCO2 rate of rise during apnea in awake subjects was determined to acquire a value that may be more applicable to awake, ventilator-dependent, critically ill patients. Clinically, apnea occurs at functional residual capacity. With FiO2 = 1.0, 20 volunteers held their breaths at functional residual capacity for 0, 10, and 20 seconds, and then for as long as possible. They exhaled through an infrared CO2 analyzer after each interval to determine end-tidal pCO2. An estimate of the logarithmic PaCO2 rise during breath holding at functional residual capacity was 7 mmHg during the first 10 seconds (43 mmHg/minute), 2 mmHg during the next 10 seconds (13 mmHg/minute), and 6 mmHg/minute thereafter. In conclusion, PaCO2 increases more rapidly in awake apneic humans than earlier thought. The values reported herein probably are better for estimating duration of apnea in conscious, critically ill patients than are values obtained during general anesthesia.