People spend more than 80% of their time indoors. In contrast to ambient air, no (legal) limits for indoor particulate matter exist, although there are WHO guidelines. In the Netherlands a measurement protocol to determine the PM2.5 in office buildings has been developed including 5 quality classes. However at the moment no simple guidelines or models are available which can support the design and in-use phases to predict the PM2.5 concentration in office buildings and schools. This paper describes the results of a mass balance model which predicts the effect of building and installation design parameters on PM2.5 concentration. Three experimental case studies are used to fit two parameters in the model and to validate the overall model. For Dutch buildings air tightness, ventilation flow and the filter quality prove to be critical factors. In the US, due to high recirculation rates, increasing the ventilation flow or reducing the infiltration flow has only a minor effect. There it is more effective to increase the filter quality. The results of our model further indicate that it is well possible for modern offices equipped with F7 filters to be below the WHO air quality guideline for annual mean PM2.5 of less than 10 μg/m3. It would be interesting to further validate the model with regard to deposition losses in offices and to include PM10 in the model for schools.