We propose a hypothesis to explain the association between daily fluctuations in ambient air pollution, especially airborne particles, and death rates that can be tested in an experimental model. The association between airborne particulates and mortality has been observed internationally across cities with differing sources of pollution, climates, and demographies and has involved chiefly individuals with advanced chronic illnesses and the elderly. As these individuals lose the capacity to maintain stable, optimal internal environments (i.e., as their homeostatic capacity declines), they become increasingly vulnerable to external stress. To model homeostatic capacity for predicting this vulnerability, a variety of regulated physiologic variables may be monitored prospectively. They include the maintenance of deep body temperature and heart rate, as well as the circadian oscillations around these set-points. Examples are provided of the disruptive changes shown by these variables in inbred mice as the animals approach death. We consider briefly the implications that the hypothesis may hold for several epidemiologic issues, including the degree of prematurity of the deaths, the unlikelihood of a threshold effect, and the role that coarse, noncombustive particles may play in the association.