A transport model that considers pore diffusion, external film resistance, finite kinetic rate and column dispersed flow, was used to mathematically describe a frontal affinity chromatography system. The corresponding differential equations system was solved in a simple and accurate form by using the numerical method of lines (MOL). The solution was compared with experimental data from literature and the analytic Thomas solution. The frontal affinity chromatography of lysozyme to Cibacron Blue Sepharose CL-6B was used as a model system. A good fit to the experimental data was made with the simulated runs of the transport model using the MOL solution. This approach was used to perform a parametric analysis of the experimental frontal affinity system. The influence of process and physical parameters on the frontal affinity chromatography process was investigated. The MOL solution of the transport model results in an unique and simple way to predict frontal affinity performance as well a better understanding of the fundamental mechanisms responsible for the separation. © 2004 Elsevier B.V. All rights reserved.