Ten adult, awake cats were exposed to high pressure (7.5, 9, or 10 MPa) of a heliox (He-O2) or trimix (He-N2-O2) gas mixture. Total duration of the experiment, i.e., duration of compression plus sojourn at maximal pressure, varied between 23 and 59 h. Throughout the experiment, minute ventilation (VE), heart rate, and rectal temperature were recorded. The total mass of gas (Mt) breathed by each animal was determined from the product of VE, gas density (p), and time (t). As previously shown, VE was increased in all animals breathing heliox mixtures, whereas this was never observed in trimix experiments. Ventilatory arrest occurred before cardiac failure in 3 animals breathing heliox mixtures, where the highest values of Mt were measured; the others survived. Rectal temperature, t, or p values did not account for the difference between those animals surviving and those who died. Thus, increased ventilation in high density gas mixtures was responsible for increased values of Mt. Present observations suggest that ventilatory failure associated to the highest values of Mt is related to respiratory muscle fatigue.