Scale-up of electrochromatographic separations has been problematic due to electrically induced heating. A two-dimensional transient temperature model for electrochromatography was developed, which accounts for physical properties of the stationary and mobile phase, and the column wall. The model also accounts for both the temperature effect on the electrical conductivity and a nonuniform, radially variant current density. This model was compared to experimental data from two electrochromatography systems with different cylindrical-column dimensions, packing materials, and operating conditions. In all cases, the model predicts the temperature to within 3°C of the actual temperature, both for column heatup and cooldown. Separation of a mixture of model proteins on the 3.81-cm-ID scale was used as the basis for scale-up calculations. The model identifies equipment parameters that control heating characteristics and can be scaled up to process 75 mL of sample per run.