The losses of righting reflex produced by various doses of phenobarbital in mice at 1 atm O2 versus 1 atm O2 plus 102 atm He were determined. The resulting dose-response curve at pressure gave an ED50 that was 64 per cent larger than the ED50 at 1 atm. This increment is essentially the same as that found for gaseous anesthetics under similar test conditions. The quantitative similarity of the results of pressure reversals of barbiturate and inhalational anesthetics suggests that the mechanisms or sites of action of these agents are similar. However, the dose-response curve at 103 atm was steeper than that at 1 atm. This raises an alternative possibility that anesthetics and pressure bear no mechanistic relationship to each other, but rather that pressure produces a generalized central nervous system stimulation that would antagonize any depressant effect.