Chronic exposure to high altitude reduces maximal O2 uptake (V̇O2(max)). At extreme altitudes approaching the summit of Mt. Everest [inspiratory PO2(PI(O2)) = 43 Torr], mean V̇O2(max) have been determined to be 15.3 ml · kg-1 · min-1 in two subjects who breathed 14% O2 at 6,300 m on Mt. Everest (West et al., J. Appl. Physiol. 54: 1188-1194, 1983). To provide a more complete description of performance near the limits of human tolerance to chronic hypoxia, we measured V̇O2(max) in volunteers in an altitude chamber before, during, and after a 40-day decompression to a barometric pressure (PB) of 240 Torr (PI(O2) = 43 Torr). In five of eight subjects studied at sea level and PB of 464, 347, 289, and 240 Torr, V̇O2(max) was reduced from 4.13 to 1.17 l/min (49.1 - 15.3 ml · kg-1 · min-1) in agreement with the prior study. Although the range decreased, the rank order among the subjects was preserved. Arterial O2 saturation at maximum effort decreased (46% by ear oximetry), but minute ventilation, respiratory frequency, and tidal volume did not. The highest minute ventilation (201 l/min BTPS) was observed at PB of 464 Torr. Arterial PCO2 in three subjects at PB of 240 Torr, at rest, and with maximum effort, averaged 10.3 and 9.6 Torr, respectively. Sustained hyperventilation was crucial to exercise performance during chronic, severe hypoxemia. V̇O2(max) was lower after altitude exposure compared with initial sea level values, indicating that exposure had not improved sea level exercise capacity.