The results of our experiments in the light of other available experimental evidence lead us to the following conclusions: (1) The metabolic acceleration in a helium atmosphere is due primarily to the thermal properties of that gas, mediated to some extent by increases in spontaneous activity. Helium may cause a transient decrease in red cell indexes, and this too is likely to be due to the thermal stress. (2) Oxygen consumption is slightly reduced on exposure to a low pressure, pure oxygen atmosphere that provides a normal alveolar oxygen tension. This effect is intimately interrelated with changes in evaporative water loss and activity and may be caused by the thermodynamic properties of this gaseous environment. (3) A neon-oxygen atmosphere shows no immediately obvious biological hazard for exposures of up to one week, and along with helium this gas appears to offer some protective advantage in altitude decompression. A suitable neon-oxygen atmosphere at half an atmosphere total pressure would have thermal properties akin to air and experimentally seems indeed to possess some of the theoretical advantages proposed for it (Bond, 1963; Roth, 1966). (4) The question of whether light inert gases such as helium and nitrogen exert molecular effects at atmospheric and subatmospheric pressures is still unresolved as is the enigma of an absolute ‘metabolic’ requirement of mammals for gaseous nitrogen.