The objective of this study is to compare the reactivity of two polymorphs of flufenamic acid with ammonia and relate it to crystal packing. Forms I and III of flufenamic acid were exposed to dry ammonia vapor. Optical microscopy, microscopic Raman, and XRPD were used to characterize the possible changes. The different reactivity of Forms I and III was clearly observed under dry ammonia vapor from 12% ammonium hydroxide. Single crystals of Form I gradually became opaque within 180 min, whereas single crystals of Form III retained transparent. FT-Raman analysis revealed that significant ammonium salt was formed at the major face of Form I, while the reaction of Form III was undetectable. So Form I is more reactive than Form III at ambient temperature, which agrees with their thermodynamic order. At 60degreesC, the thermodynamic order switches and Form I is the stable form. However, Form I is still more reactive with ammonia than Form III at 60degreesC. The reaction rate is likely to be determined more by kinetic factors. The good accessibility of reaction groups could be one of the reasons that Form I is more reactive.