Quantitative structure–retention relationships (QSRR) have been employed in studying the molecular mechanism of chromatographic separations under pressure- (HPLC) and electro-driven (CEC) conditions. Logarithms of retention factors corresponding to zero percent of organic modifier in aqueous eluent, log k , were determined on eight reversed-phase w stationary phases under both HPLC and CEC conditions at similar eluent flow velocities. QSRR equations describing log kw in terms of linear solvation energy relationship (LSER) parameters of analytes, in terms of simple structural descriptors acquired by calculation chemistry, and in terms of logarithms of n-octanol–water partition coefficients, were derived. Parameters of corresponding QSRR equations for individual stationary phases were compared for both HPLC and CEC modes and the resulting similarities and differences in retention mechanisms were discussed. It has been concluded that at least in the case of regular neutral analytes the specific inputs to separation mechanism due to the electric field in CEC are of secondary importance.