The sensitivities of groundwater-streamflow interaction to global climate change over the medium-sized mountainous Mesochora catchment in central Greece have been analysed. The global climate change was simulated through a set of hypothetical and monthly GISS (Goddard Institute for Space Studies) scenarios of temperature increases coupled with precipitation changes. The catchment hydrological regime, which is dominated by spring snowmelt runoff, was simulated by the coupling of the snowmelt and soil moisture accounting models of the US National Weather Service River Forecast System (US NWSRFS). The groundwater was represented through a lower zone one-tension water storage and two free water storages parameterized by the soil moisture model, while the streamflow was the sum of direct runoff, surface runoff and interflow from the upper zone free water, plus the primary and secondary baseflows yielded by the model. The interaction between groundwater and streamflow was expressed by the ratio of the two variables on a seasonal and monthly basis. Both representations of global climate change resulted in a moderate influence on the groundwater-streamflow interaction during the winter months and in a very high one in the spring and summer months. In particular, the major seasonal shift in the snow accumulation pattern related to climate change, as well as the large runoff reduction and evapotranspiration increase occurring in spring and summer months, boosted considerably the groundwater to streamflow ratio. This latter would probably have negative impacts on various problems of water resources management (e.g. droughts, water supply, irrigation, water pollution).