Four men, exposed to the pressure equivalent of 1,200 ft of seawater (37 ATA) for 6 days in a CO2-free, normoxic helium-oxygen environment (Predictive Studies III-1971, Aviation Space Environ. Med. 4: 843-855, 1977), had no evident respiratory distress at work, at rest, or asleep. Ventilatory responses of two men to CO2 were measured in 20-min acute exposures to mixtures of oxygen (173 Torr) with nitrogen, crude neon, and helium over a gas density range of 0.4-22 g/l and a pressure range of 1-37 ATA during stepwise compression of 37 ATA. Analysis of delta V/delta PACO2 as functions of pressure, of density, and of density-to-viscosity ratios shows that increased gas density, but not nitrogen narcosis, is associated with gross diminution of the ventilatory response to CO2. A small ventilatory response to CO2 is predicted for liquid breathing when viscosity is included as a parameter in the analysis. Other findings associated with increased gas densities and progressive elevation of inspired CO2 concentration are disruption of the normal patterns of tidal volume and frequency of breathing and reduction in the range of linear respiratory response to CO2.