The use of co-amorphous systems for solubility enhancement of poorly water-soluble drugs has recently gained interest in the field of pharmaceutical technology. However, undesired co-amorphisation of a drug may lead to an alteration of the performance of the drug product, e.g. the previously observed co-amorphisation of indomethacin and arginine upon storage of tablets containing both components in an initially crystalline form at room temperature (RT) and 75 % relative humidity (RH). Therefore, the aim of the present study was to further investigate this unintended co-amorphisation by storing plain crystalline γ-indomethacin and arginine as well as physical mixtures of both components at RT and three different RH levels (28, 58, and 75 % RH). After storage for up to 101 days, their properties were analysed by X-ray powder diffraction, infrared spectroscopy, differential scanning calorimetry, thermogravimetric analysis, and HPLC. Results showed that the solid state of plain γ-indomethacin did not change during storage at all three storage conditions. In contrast, arginine was found to form a dihydrate upon storage at RT/58 % RH and RT/75 % RH. The physical mixtures, stored at RT/28 % RH and RT/58 % RH, remained crystalline and were chemically stable, while the formation of a co-amorphous salt between indomethacin and arginine as well as basic hydrolysis of indomethacin started already 1 day after exposure to RT/75 % RH. Moreover, formation of a crystalline salt of indomethacin and arginine upon storage at RT/75 % RH was observed. As neither of these instabilities occurred, if indomethacin was stored separately, the simultaneous effects of arginine and moisture on the solid state properties and chemical stability of indomethacin should be taken into account, if selecting arginine as excipient.