Chromatographic methods using chiral stationary phases have been developed for the separation of fluoxetine hydrochloride enantiomers. Ovomucoid and tris(3,5-dimethylphenyl carbamate) cellulose stationary phases were used in the reversed- and normal-phase modes, respectively. Acceptable isomer separation was achieved at pH 3.5 with the ovomucoid phase. Isopropyl alcohol and methyl-tert- butyl ether mobile phase modifiers each provide complete resolution using the derivatized cellulose column. Better separation robustness was obtained with a column temperature of 1 degree C the isopropyl alcohol modifier. The methyl-tert-butyl ether system was robust at room temperature. Differences in relative enantiomer amounts of as little as 2% could be determined. The chromatographic conditions provided a much more discriminating test compared to an optical rotation method proposed for pharmacopeial use which had difficulty distinguishing individual enantiomers. The chiral chromatographic conditions were also applied to capsule formulations to demonstrate the presence of racemic fluoxetine hydrochloride.