For hydrophilic organic solids, it is well recognized that degradation is often promoted by exposure to humid conditions. Although this is an important issue for certain classes of materials, in particular pharmaceuticals, the factors which dictate the sensitivity of a given compound to moisture are not well understood. The goal of this work was to elucidate the synergistic influence of self-originating impurities and water vapor on the degradation kinetics of the histamine H2 receptor antagonist, ranitidine HCl. Physical mixtures of the drug and each of three major degradation products were subjected to conditions of elevated temperature and relative humidities. Pure samples showed a sigmoidal-shaped degradation profile for all storage conditions studied. During the lag time, the pure drug gained minimal quantities of moisture. Once degradation commenced, the samples started to absorb moisture. When mixed with the degradant, the lag period was eliminated for all storage conditions, even at low partial pressures of water. The extent of moisture gain by samples containing impurities could not be attributed to the presence of the impurity alone. It was found that the presence of impurities in contact with the surface of the drug, in combination with water vapor, promoted a phase transition of the crystalline material to the solution phase. A ternary phase diagram was constructed to visualize the proportion of the drug in the solid and solution phases as a function of impurity and moisture content. The increased mobility of molecules in solution presumably leads to enhanced reactivity relative to the crystalline material.