Ultraviolet germicidal irradiation (UVGI) systems are known to be effective in the control of harmful microorganisms in the indoor environment. This paper addresses the modelling of induct airstream disinfection with a methodology that couples an energy model driven multizone airflow and contaminant transport model to simulate the deactivation of anthrax spores. An example based on a 1,900 m2 commercial building with a forced-air heating, ventilating, and air-conditioning system is used to illustrate the application of the methodology. Representative releases of anthrax are simulated under different conditions to study the variation of effectiveness of UVGI during transient conditions. The practical application of the approach is discussed.