The role of methanol produced in-situ in the liquid phase methanol synthesis process has been experimentally examined. The catalyst crystallite size is found to be more stable when the produced water and methanol are consistently removed from the catalyst active sites. The experimental evidence shows that in-situ produced water is not the only culprit for the catalyst crystallite size growth, rather, methanol is also responsible for contributing to crystallite growth and therefore catalyst deactivation. Hydrothermal leaching of the catalyst was also determined to be an active participant in catalyst deactivation. Two experimental designs were run to assess the influence of temperature, leaching solution concentration and pretreatment conditions on the extent of leaching of the methanol synthesis catalyst. Water and methanol were found to be active participants in the reduction of catalyst activity. Hence, the methanol/water solutions serve as potentially harmful agents in the leaching of aluminum and copper from the synthesis catalyst.