A general numerical method is developed for multicomponent chromatography for the case where a pH gradient occurs and several buffering species are present that become adsorbed together with the components being separated through an ion-exchange mechanism. Acid-base equilibrium relations are used to determine the ionic compositions in the liquid and adsorbed phases and are solved using a single-variable Newton’s method. The differential material-balance relations are integrated numerically using the method of characteristics. The transport relations are incorporated using a matrix analog of the linear-driving-force approximation. The resulting method accounts for the adsorption of each ionic form of each buffering species, for multicomponent diffusional interactions arising from induced electric fields, for volume and concentration overloading of proteins, and for changes in. the adsorption capacity caused by pH variations. Numerical calculations illustrate factors governing the selection of the adsorbent and buffer components for use in separating mixtures of proteins using retained, internally generated pH gradients.