Summary The behavior of 5,5-disubstituted hydantoin derivatives has been studied using four chromatographic systems, two normal-phase (silica gel stationary phase with ethyl acetate–toluene and acetonitrile–toluene mobile phases) and two reversed-phase (RP-18 systems with methanol–water and acetonitrile–water mobile phases). The effect of the structures of the derivatives on their retention in both normal and reversed-phase modes was investigated by use of QSRR and molecular descriptors. By means of multiple linear regressions results were interpreted in terms of understandable and physically meaningful variables. Among six models proposed, the two best were selected and tested for prediction of retention – one for normal-phase chromatography (NPC) and the other for reversed-phase chromatography (RPC). The most informative properties in the best NPC model, with similar effects on retention, are log P and valence connectivity indices. The informative properties in the best RPC model were log P and molecular weight, but the statistics was much worse than for NPC. Cross-validation indicated the best models are reliable QSRR models.