Aerenchyma tissues form gas-conducting tubes that provide roots with oxygen under hypoxic conditions. Although aerenchyma have received considerable attention in Zea mays, the signaling events and genes controlling aerenchyma induction remain elusive. Here, we show that Arabidopsis thaliana hypocotyls form lysigenous aerenchyma in response to hypoxia and that this process involves H(2)O(2) and ethylene signaling. By studying Arabidopsis mutants that are deregulated for excess light acclimation, cell death, and defense responses, we find that the formation of lysigenous aerenchyma depends on the plant defense regulators LESION SIMULATING DISEASE1 (LSD1), ENHANCED DISEASE SUSCEPIBILITY1 (EDS1), and PHYTOALEXIN DEFICIENT4 (PAD4) that operate upstream of ethylene and reactive oxygen species production. The obtained results indicate that programmed cell death of lysigenous aerenchyma in hypocotyls occurs in a similar but independent manner from the foliar programmed cell death. Thus, the induction of aerenchyma is subject to a genetic and tissue-specific program. The data lead us to conclude that the balanced activities of LSD1, EDS1, and PAD4 regulate lysigenous aerenchyma formation in response to hypoxia.