OBJECTIVE： To establish a method for separating of 4 kinds of H1-receptor antagonist enantiomers as cetirizine hydrochloride， promethazine hydrochloride， terfenadine and pheniramine maleate. METHODS： HPLC method was adopted. Chiralcel OJ-H chiral column was selected. Detection wavelength was set at 230 nm； column temperature was room temperature； flow rate was 1.0 mL/min； sample size was 20 μL. Using retention time， selective factors and separation rate as indexes， the influence of acid-base additives （diethylamine）， type and ratio of organic modifiers （ethanol， isopropanol）， methanol on the separation of 4 kinds of enantiomers in mobile phase were investigated. RESULTS： The results of mobile phase investigation was the mobile phase of cetirizine hydrochloride and promethazine hydrochloride was n-hexane and ethanol （90 ∶ 10， V/V）. Mobile phase of terfenadine was n-hexane-methanol-ethanol-diethylamine （89 ∶ 9.9 ∶ 1 ∶ 0.1， V/V/V/V）. Mobile phase of pheniramine maleate enantiomers was n-hexane-methanol-ethanol-diethylamine （98 ∶ 2 ∶ 0.5 ∶ 0.1， V/V/V/V）. Under the condition， 4 kinds of drug enantiomers were separated completely， with separate rate of 4.36， 3.76， 1.55， 1.71. CONCLUSIONS： Established Chiralcel OJ-H chiral column-HPLC is selective for these 4 kinds of H1-receptor antagonists， and can be used for the chiral separation of the enationmers.