Reactive oxygen intermediates (ROIs) regulate apoptosis during normal development and disease in animals. ROIs are also implicated in hypersensitive resistance responses of plants against pathogens. Arabidopsis Isd1 mutants exhibited impaired control of cell death in the absence of pathogen and could not control the spread of cell death once it was initiated. Superoxide was necessary and sufficient to initiate lesion formation; it accumulated before the onset of cell death and subsequently in live cells adjacent to spreading Isd1 lesions, Thus, runaway cell death seen in Isd1 plants reflected abnormal accumulation of superoxide and lack of responsiveness to signals derived from it.