Hypercapnia evokes an uncomfortable sensation, termed 'air hunger'. We examined the relationship between PETCO2 and ratings of air hunger intensity under three conditions in 16 subjects: 1) mechanical ventilation with hyperoxic gas mixtures at fixed frequency and tidal volume (twice resting ventilation), 2) the same mechanical ventilation, but with hypoxic gas mixture, 3) spontaneous breathing with hyperoxic gas mixture. In each case, PETCO2 was varied randomly among several levels, each held for 5 min. During hyperoxic mechanical ventilation, the mean threshold for air hunger sensation was 43 Torr, i.e., 4 Torr above resting PETCO2; intolerable air hunger was evoked by 50 Torr. The threshold and tolerable levels of PETCO2 varied among individuals, but were not well correlated with their ventilatory responses to CO2. Hypoxia (PETO2 60-75 Torr) shifted the PETCO2 at both threshold and tolerance down by only 2 Torr. Breathing greatly reduced the air hunger experienced at any given PETCO2 (threshold increased 5 Torr, and sensitivity decreased 50%).