The long term hydrological response of a medium-sized mountainous catchment to climate changes has been examined, The climate changes were represented by a set of hypothetical scenarios of temperature increases coupled with precipitation and potential evapotranspiration changes. Snow accumulation and ablation, plus runoff from the study catchment (the Mesochora catchment in central Greece) were simulated under present (historical) and altered climate conditions using the US National Weather Service snowmelt and soil moisture accounting models. The results of this research obtained through alternative scenarios suggest strongly that all the hypothetical climate change scenarios would cause major decreases in winter snow accumulation and hence increases in winter runoff, as well as decreases in spring and summer runoff. The simulated changes in annual runoff were minor compared with the changes in the monthly distribution of runoff. Attendant changes in the monthly distribution of soil moisture and actual evapotranspiration would also occur. Such hydrological results would have significant implications on future water resources design and management.