Abstract: AIM　To investigate the enantioselective pharmacokinetic process of benproperine in healthy volunteers. METHODS　An enantiospecific HPLC method was developed and used to determine the plasma concentrations of each enantiomer. Six healthy Chinese male volunteers received an oral dose of 60 mg (±)-benproperine. The ratios of the enantiomers in plasma samples were measured on a chiral AGP column. The plasma concentration of each enantiomer was then calculated using the ratios of enantiomers and total concentration of the two enantiomers previously measured. RESULTS　The plasma levels of (-)-(S)-benproperine were always significantly higher than those of its antipode in six volunteers. The mean AUC_0-t and C_max values for (-)-(S)-benproperine were 2.18 and 2.12 times higher than those of (+)-(R)-benproperine. There was no significant difference between the T_1/2 for both enantiomers, tested by paired t test (P>0.05). Half an hour after administration of benproperine, the S/R ratio in plasma samples was as high as 3.8, and in 2 hours it drastically decreased to about 2.2, then kept on till 24 hours. CONCLUSION Benproperine showed significant enantioselective pharmacokinetics in the human after an oral dose of the racemate.