As climate is a key agro-ecosystem driving force, climate change could have a severe impact on agriculture. Many assessments have been carried out to date on the possible effects of climate change (temperature, precipitation and carbon dioxide concentration changes) on plant physiology. At present however, likely effects on plant pathogens have not been investigated deeply. The aim of this work was to simulate future scenarios of downy mildew (Plasmopara viticola) epidemics on grape under climate change, by combining a disease model to output from two general circulation models (GCMs). Model runs corresponding to the SRES-A2 emissions scenario, characterized by high projections of both population and greenhouse gas emissions from present to 2100, were chosen in order to investigate impacts of worst-case scenarios, among those currently available from IPCC. Three future decades were simulated (2030, 2050, 2080), using as baseline historical series of meteorological data collected from 1955 to 2001 in Acqui Terme, an important grape-growing area in the north-west of Italy. Both GCMs predicted increase of temperature and decrease of precipitation in this region. The simulations obtained by combining the disease model to the two GCM outputs predicted an increase of the disease pressure in each decade: more severe epidemics were a direct consequence of more favourable temperature conditions during the months of May and June. These negative effects of increasing temperatures more than counterbalanced the effects of precipitation reductions, which alone would have diminished disease pressure. Results suggested that, as adaptation response to future climate change, more attention would have to be paid in the management of early downy mildew infections; two more fungicide sprays were necessary under the most negative climate scenario, compared with present management regimes. At the same time, increased knowledge on the effects of climate change on host–pathogen interactions will be necessary to improve current predictions.