Entomopathogenic nematode, Steinernema carpocapsae, carries the symbiotic bacterium, Xenorhabdus nematophita, and enter host insect hemocoel. In the infected host, nematodes release the bacteria, which in turn cause lethal hemolymph septicemia. This study was designed to test a hypothesis that hemolymph septicemia of beet armyworm, Spodoptera exigua, is triggered by X. nematophita through a programmed cell death (=apoptosis) of the hemocytes. Morphological changes of the hemocytes after the bacterial infection were similar to cell changes undergoing a typical apoptosis. At 4-8 h post-infection, the cell membrane blebbing and apoptotic vesicles were observed and the nuclear membrane was broken apart. At 12 h post-infection, the overall cell shape was lost externally and nuclear condensation was evident internally, where genomic DNA was fragmented into small pieces. Proportion of apoptotic hemocytes increased with post-infection time and reached a maximum level when the hemocytes were in complete septicemia. Increase of FAD-glucose dehydrogenase (EC 1.1.99.10) activity preceded initial hemocyte apoptosis after the bacterial infection. The infected plasma or the culture broth of X. nematophila contained apoptosis-inducing factors. The apoptosis factors were extracted into organic fraction and turned out to be relatively high hydrophobic chemical nature after further fractionation assay. These results indicate that X. nematophita induces hemocyte apoptosis by its secretory material(s), which lead to hemolymph septicemia and immunodepression of the target insect hosts.