This work presents a two-population model describing the competition of anodophilic and methanogenic microbial populations for a common substrate in a microbial fuel cell (MFC). Fast numerical solution of the model is provided by using ordinary differential equations to describe biomass growth and retention in the anodic compartment. The model parameters are estimated and validated using experimental results obtained in four continuous-flow air-cathode MFCs operated at various external resistances and organic loads. Model analysis demonstrates the influence of operating conditions on MFC performance and suggests ways to maximize MFC power output. The model is suitable both for process optimization and on-line control applications. Crown Copyright (C) 2010 Published by Elsevier Ltd. All rights reserved.