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Early experimental work, conducted at Defence R and D Canada Suffield, measured and characterized the personal and environmental contamination associated with simulated anthrax-tainted letters under a number of different scenarios in order to obtain a better understanding of the physical and biological processes for detecting, assessing, and formulating potential mitigation strategies for managing the risks associated with opening an anthrax-tainted letter. These preliminary experimental investigations have been extended in the present study to simulate the contamination from anthrax-tainted letters in an Open-Office environment using Computational Fluid Dynamics (CFD). A quantity of 0.1 g of a biological simulant Bacillus globigii (BG) for anthrax was released from an opened letter in the experiment. The accuracy of the model for prediction of the spatial distribution of BG spores in the office from the opened letter is assessed qualitatively (and to the extent possible, quantitatively) by detailed comparison with measured BG concentrations obtained under a number of scenarios, some involving people moving within the office. It is hypothesized that the discrepancy between the numerical predictions and experimental measurements of concentration were mainly caused by :(1) air flow leakage from cracks and crevices in the walls and windows of the building shell; (2) decoupling between the present CFD simulation and dispersion of BG spores in the Heating, Ventilation, and Air Conditioning (HVAC) system; (3) the effect of deposition and re-suspension of BG spores not being considered in the present CFD simulations. Although there is still a scope of further improvement in the present CFD simulation, it should be emphasized here that the advantages of utilization of CFD modeling for assessment and design of mitigation strategies and protocols for defence against anthrax-tainted letters over an experimentally based approach to the problem are obvious: