Abstract The behavior of interacting macromolecules undergoing transport on molecular sieve columns (gel chromatography) has been investigated by computer simulation. Equations for chromatographic transport of multicomponent interacting solutes have been formulated to include axial dispersion effects within gel columns. Useful frames of reference for the expression of concentration, solute fluxes, and equilibrium constants have been described and flow equations for the total column volume frame of reference have been developed in detail. In this frame of reference, solute concentrations and fluxes are represented with respect to the total column as it would be seen by direct optical scanning. Relationships are presented which transform quantities from this frame of reference into corresponding quantities in the free solution frame of reference, which is most suitable for the description of elution chromatography. Numerical solutions of the flow equations have been obtained by the simulation method of Cox (Cox, D. J., Arch. Biochem. Biophys., 129, 106 (1969)). Resulting concentration profiles are presented for a reversibly dimerizing system. Axial dispersion coefficients and other column parameters used in the simulations are based on typical experimental values and experimentally verified relationships. The parameters investigated by simulation include development time, column flow rate, degree of molecular association, gel porosity, and gel particle size.