This review of available literature attempts to interpret net effects of metabolically inert light gases (He, H2, and Ne) as the resultant of hydrostatic pressure and intrinsic pharmacological effects associated with exposure to these gases, and to assess the relative importance of each component with respect to a number of biological responses. A common pattern is recognizable for pressure reversal of anesthesia, high pressure convulsions, high pressure bradycardia, and certain characteristics of liposome model systems. Using the method of analysis proposed, these lightest gases can be shown to conform to the pattern of relation of potency to physical properties characteristic of more potent gaseous anesthetics, including N2, N2O, and Xe. The relations between effect produced and partial pressure of the acting gas are approximately linear to total pressures of 100 ATA for anesthesia or pressure reversal of anesthesia and (or to a much smaller extent) for the liposome model systems, but not for high pressure convulsions. As a result of these general factors no single gas can be expected to neutralize the effects of hydrostatic pressure with regard to all of the biological responses tested over any significant pressure range. A series of experiments with single cells and tissue cultures have revealed interactions between high pressure and inert gas that do not conform to the pattern set by the responses mentioned so far. These responses cannot yet be shown to constitute a homogeneous group and may represent at least two subgroups. Responses falling into this second heterogeneous category include cell motility, development of cell abnormalities and lysis, and cell and perhaps virus replication or multiplication. The implication of these results for the formulation of biophysical hypotheses to explain interactions between inert gas and high pressure, for considerations of high pressure effects as a safety hazard, and for the problem of experimental approaches to the study of pressure acclimation are discussed briefly.