Accelerated thermal, hydrolytic, and photochemical degradations of alprazolam were performed under several reaction conditions. The stress studies revealed the photolability of the drug as the most adverse stability factor; the main photodegradation products were isolated and properly characterized as: triazolaminoquinoleine; 5-chloro-[5‵‵-methyl-4H-1,2,4-triazol-4-yl]benzophenone, and 1-methyl-6-phenyl-4H-s-triazo-[4,3-α][1,4]benzodiazepinone. Accelerated pH-dependent studies show that the photoinstability increases as the pH decreases; at pH 9.0, photodegradation does not occur, therefore, the photochemical degradation of alprazolam was performed in buffered solutions at pH 2.0 and 3.6. The higher rate of reaction was observed at pH=2.0; consequently, acidic conditions should be avoided and appropriate light protection is recommended during the drug-development process, storage, and handling. The main degradation route for alprazolam tablets is also photochemical. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:1274–1286, 2002