A simple, selective, precise, and stability-indicating high-performance thin-layer chromatographic (HPTLC) method has been established and validated for analysis of duloxetine hydrochloride in formulations. The compound was resolved on aluminum-backed silica gel 60 F254 plates with toluene-methanol-10% (v/v) ammonia 3:1.3:0.05 (v/v) as mobile phase. This system was found to give compact spots for duloxetine hydrochloride (RF 0.39 ± 0.02). Densito-metric analysis of duloxetine hydrochloride was performed at 231 nm. Regression analysis data for the calibration plots were indicative of good linear relationships between response and concentration over the range 60-480 ng per band. The correlation coefficient was 0.9981. The slope and intercept of the calibration plot were 8.2229 ± 0.22 and 458.93 ± 7.21 respectively. The method was validated for precision and recovery. The limits of detection and quantification were 20 ± 0.51 and 60 ± 1.05 ng per spot, respectively. Duloxetine hydrochloride was subjected to acid, base, peroxide, dry heat, wet heat, and photodegradation (sunlight). In stability tests the drug was susceptible to acidic and basic hydrolysis, oxidation, and photodegradation. Statistical analysis proved the method is repeat-able, selective, and accurate for estimation of duloxetine hydrochlo-ride. Because the method could effectively separate the drug from its degradation products, it can be used as a stability-indicating method. For separation and analysis of duloxetine hydrochloride and olanzapine in a synthetic mixture, acetone-methanol-triethyl-amine 5:3:0.5 (v/v) was used as mobile phase. Spot detection was performed at 240 nm. The RFvalues were 0.63 ± 0.02 and 0.77 ± 0.02, respectively. The method was validated for linearity, accuracy, and precision. Calibration plots were linear over the ranges 100-800 and 50-400 ng per band, respectively. The method was successfully used for separation and analysis of duloxetine hydrochloride and olanza-pine in a synthetic mixture.