Cetirizine hydrochloride is a non-sedating H1-receptor antagonist used in patients whit urticaria and allergic rhinitis. It is frequently administrated as racemate; although recent data demonstrate that the antihistaminergic activity of the racemate is primarily due to the levo-enantiomer, while dextrocetirizine failed to demonstrate any significant activity. Moreover levocetirizine exhibits a more pharmacokinetic behaviour due to a lower volume of distribution and a slower renal clearance; therefore cetirizine has been recently marked as levo- enantiomer (Xyzal) in Europe. In order to study the simultaneous determination of (+)- and (-)- cetirizine hydrochloride we have developed direct separation methods by HPLC on polysaccharide-based chiral stationary phases. Satisfactory results were achieved on a Chiralcel OD-R column under gradient elution whit a mobile phase of acetonitrile and perchlorate buffer (0.3M; pH 3.30); these conditions allowed the complete enantioseparations (Rs= 1.65) of the analyte in times suitable for routine analyses. Complete separations in short analysis time (Rs= 1.61) were performed on a Chiralcel OD column under isocratic normal phases conditions (85% n-hexane and 15% ethanol, containing 0.15% trifluoroacetic acid). These conditions were applied to the determination of the stability of cetirizine hydrochloride in methanolic solutions and our studies revealed the formation of an achiral and a chiral degradation product. The developed procedures could be of interest for routine analyses and stereoselective investigations.