SummaryPermethylated P-cyclodextrin (hereafter designated perMe-P-CD), diluted or not in polysiloxane, is an efficient chiral discriminant for native, 3-methylated, and 1,3-dimethylated series of 5-methyl-5-(CnHzn+l)hydantoins. From thermodynamic data obtained with pure perMe-P-CD and with the aid of molecular modeling, it is concluded that: (i) For native hydantoin derivatives having a carbon chain at the 5-position varying from ethyl to nonyl (2 I n I 9), the retention time is related to their H-bonding capability. The resolution is poor for derivatives with n 5 4. For n 2 5, the resolution is considerably improved and this increase in resolution is attributed to the long alkyl chain being capable of being buried inside the cyclodextrin cavity. (ii) For 1,3-dimethylhydantoin derivatives having a carbon chain at the 5-position varying from ethyl to hexyl (2 In 16), the retention time is mainly determined by a steric fit between the solute and the inner volume of the macrocyclic cavity. For n = 2, a particular behavior is observed, consistent with a total inclusion of the solutes inside the cavity. By contrast with the native hydantoins, the selectivity is high for light derivatives. Thus, the selectivity does not correlate with a strong docking energy (such as the presence of H-bonds postulated with native derivatives). (iii) For 3-methylhydantoin derivatives having a carbon chain at the 5-POsition varying from ethyl to octyl (21 nI8), as expected, retention time and selectivity are intermediate between that of native hydantoins and 1,3-dimethylhydantoins. For all three series, where n 2 5, the increase in chain length ( n ) does not bring about substantial changes in the chromatographic results. Therefore, for these long alkyl chain derivatives, similar dominant interactions with perMe-P-CD are postulated.