This paper describes the development of a stability-indicating RP-HPLC method for duloxetine hydrochloride (DLX) in the presence of its degradation products generated from forced decomposition studies. The drug substance was found to be susceptible to stress conditions of acid, base, oxidation, wet heat, dry heat, and photodegradation. The drug was found to be stable to the dry heat condition attempted. Successful separation of the drug from the degradation products formed under stress conditions was achieved on a Phenomenex C18 column (250 x 4.6 mm id, 5 microm particle size) using acetonitrile-methanol-0.032 M ammonium acetate buffer (55 + 05 + 40, v/v/v) as the mobile phase at a flow rate of 1.0 mL/min at 40 degrees C temperature. Quantification was achieved with photodiode array detection at 290 nm over the concentration range 0.2-5 microg/mL with mean recovery of 101.048 +/- 0.53% for DLX by the RP-HPLC method. Statistical analysis proved the method is repeatable, specific, and accurate for estimation of DLX. Because the method could effectively separate the drug from its degradation products, it can be used as a stability-indicating method.