A mathematical model was developed and validated to simulate the dynamic behavior of a UASB reactor. This model took into consideration all the biological and physicochemical reactions. Seven microbial populations were selected using Monod kinetics where inhibition terms were added. The overall biological reactions were determined by first evaluating the reactions for energy and synthesis separately and then adding them together. For each differential time interval, the biomass produced was estimated from the stoichiometry of these reactions. The feasibility of each reaction was determined by thermodynamic calculations. A thermodynamic solution was suggested for the microorganisms that are able to follow more than one catabolic routes and produce several products in spite of the fact that they consume just one substrate. All the reactions that may be performed were realized according to the relative percentage of their free energies. The validation of the model was based on a set of dynamical experiments designed to cover a wide spectrum of operating conditions that are likely to take place in the practical Operation of a UASB plant. The model can be a useful tool for the prediction of process performance in transient conditions, even in failure, and can be used to assist in the operation of biogas plants. 9 2007 American Institute of Chemical Engineers AIChE J, 53: 32693276,2007.