Using a model plant Nicotiana benthamiana, we have demonstrated that initial calcium uptake in response to the HR (hypersensitive response)-causing pathogen Pseudomonas syringae pv syringae 61 is followed by net calcium efflux initiated at about 12 h after the bacterial challenge and sustained for at least 48 h. Our data suggest that calcium not only acts as an important second messenger in the activation of resistance responses but may also be a downstream mediator of later cell death acceleration and completion of the defense reaction. Accordingly, we propose that the existing model of HR should be amended to include a PM Ca(2+) ATP pump as an important component of the HR to pathogens in plants.