It is inappropriate to use the assumption of instantaneously well-mixed zones to model airflows and pollutant transport in large indoor spaces. We investigate two approaches for describing the details of airflows in large indoor spaces, for accuracy and suitability for integration with multi-zone infiltration models. One approach, called the zonal method, was developed over the last 15 years to provide an improvement over the well-mixed assumption. The second approach is the use of a computational fluid dynamics simulation using a coarse grid model of the large indoor space. We compare velocity predictions from different formulations of zonal methods and coarse-grid k-e computational fluid dynamics (CFD) models, to measurements, in a 2D mechanically ventilated isothermal room. Our results suggest that, when airflow details are required, coarse-grid CFD is a better-suited method to predict airflows in large indoor spaces coupled with complex multi-zone buildings, than are the zonal methods. Based on the comparison of pressure predictions from different models, we offer guidance regarding the coupling of a model of detailed airflow in large spaces to algebraic multi-zone infiltration models.