Because of the impact that oxidizing air pollutants such as ozone (O3) may have on public health, identification of factors that influence susceptibility to exposure remains a critical issue. The role of genetic background as a susceptibility factor is becoming increasingly clear. In this paper, evidence is reviewed which suggests that susceptibility to O3 is a heritable trait in humans. Experimental studies are also described that characterize the mode of inheritance of O3-induced lung injury in inbred strains of mice. It is suggested that future investigations should strive to identify phenotypic markers of susceptibility as a means to identify individuals who are genetically at risk for the development of oxidant-induced lung injury.