Modern building ventilation design must take into account the health, safety and comfort of the occupants, as well as energy consumption and the environment. The system needs to protect occupants against chemical contaminants from numerous internal sources office equipment, furniture, building materials, appliances, as well as intentional release. A promising technology which has great potential in this respect is UV photocatalytic oxidation (UV-PCO). Designing a UV-PCO system for a building requires full understanding of its performance, which strongly depends on the UV intensity field, types and concentration levels of reactants, oxygen and moisture levels, temperature, reflectance of duct surfaces, system configuration, orientation, air stream characteristics like temperature, humidity, air velocity and mixing, just to mention a few. This paper reports the development of a mathematical model for predicting the performance of a honeycomb monolith PCO reactor used in building mechanical ventilation systems. The model is validated by comparing its prediction with experimental data and with the prediction made by an existing model. The influence of several kinetic parameters such as airflow rate, pollutant inlet concentration, light intensity, humidity and catalyst deactivation has been investigated. The developed model can be used as a practical tool to simulate and optimize a UV-PCO system for application in building mechanical ventilation system. (C) 2011 Elsevier Ltd. All rights reserved.