Rapid and localized programmed cell death, known as the hypersensitive response (HR) is frequently associated with plant disease resistance. In contrast to our knowledge about the regulation and execution of apoptosis in animal system, information about plant HR is limited. Recent studies implicated the mitogen-activated protein kinase (MAPK) cascade in regulating plant HR cell death as well as several other defense responses during incompatible interactions between plants and pathogens. Here, we report the generation of transgenic Arabidopsis plants that express the active mutants of AtMEK4 and AtMEK5, two closely related MAPK kinases under the control of a steroid-inducible promoter. Induction of the transgene expression by the application of dexamethasone, a steroid, leads to HR-like cell death, which is preceded by the activation of endogenous MAPKs and the generation of hydrogen peroxide. Both prolonged MAPK activation and reactive oxygen species generation have been implicated in the regulation of HR cell death induced by incompatible pathogens. As a result, we speculate that the prolonged activation of the MAPK pathway in cells could disrupt the redox balance, which leads to the generation of reactive oxygen species and eventually HR cell death.