A modular system for source-to-dose-to-effect modeling analysis has been developed based on the modeling environment for total risk studies (MENTOR),((1)) and applied to study the impacts of hypothetical atmospheric releases of anthrax spores. The system, MENTOR-2E (MENTOR for Emergency Events), provides mechanistically consistent analysis of inhalation exposures for various release scenarios, while allowing consideration of specific susceptible subpopulations (such as the elderly) at the resolution of individual census tracts. The MENTOR-2E application presented here includes atmospheric dispersion modeling, statistically representative samples of individuals along with corresponding activity patterns, and population-based dosimetry modeling that accounts for activity and physiological variability. Two hypothetical release scenarios were simulated: a 100 g release of weaponized B. anthracis over a period of (a) one hour and (b) 10 hours, and the impact of these releases on population in the State of New Jersey was studied. Results were compared with those from simplified modeling of population dynamics (location, activities, etc.), and atmospheric dispersion of anthrax spores. The comparisons showed that in the two release scenarios simulated, each major approximation resulted in an overestimation of the number of probable infections by a factor of 5 to 10; these overestimations can have significant public health implications when preparing for and responding effectively to an actual release. This is in addition to uncertainties in dose-response modeling, which result in an additional factor of 5 to 10 variation in estimated casualties. The MENTOR-2E system has been developed in a modular fashion so that improvements in individual modules can be readily made without impacting the other modules, and provides a first step toward the development of models that can be used in supporting real-time decision making.