A mathematical model was developed to describe the anaerobic ammonium oxidation (ANAMMOX) process in a granular upflow anaerobic sludge blanket (UASB) reactor. ANAMMOX granules were cultivated in the UASB reactor by seeding aerobic granules. The granule-based reactor had a great N-loading resistant capacity. The model simulation results on the I-year reactor performance matched the experimental data well. The yield coefficient for the growth and the decay rate coefficient of the ANAMMOX granules were estimated to be 0.164 g COD g(-1) N and 0.00016 h(-1), respectively. With this model, the effects of process parameters on the reactor performance were evaluated. Results showed that the optimum granule diameter for the maximum N-removal should be between 1.0 and 1.3 mm and 3 that the optimum N loading rate should be 0.8 kg N m(-3) d(-1). In addition, the substrate micro-profiles in the ANAMMOX granules were measured with a micro-electrode to explore the diffusion dynamics within the granules, and the measured profiles matched the predicted results well. Biotechnol. Bioeng. 2009;103: 490-499. (C) 2009 Wiley Periodicals, Inc.