Wolbachia, a maternally transmitted microorganism of the Rickettsial family, is known to cause cytoplasmic incompatibility, parthenogenesis, or feminization in various insect species. The bacterium-host relationship is usually symbiotic: incompatibility between infected males and uninfected females can enhance reproductive isolation and evolution, whereas the other mechanisms enhance progeny production. We have discovered a variant Wolbachia carried by Drosophila melanogaster in which this cozy relationship is abrogated. Although quiescent during the f ly's development, it begins massive proliferation in the adult, causing widespread degeneration of tissues, including brain, retina, and muscle, culminating in early death. Tetracycline treatment of carrier f lies eliminates both the bacteria and the degeneration, restoring normal life-span. The 16s rDNA sequence is over 98% identical to Wolbachia known from other insects. Examination of laboratory strains of D. melanogaster commonly used in genetic experiments reveals that a large proportion actually carry Wolbachia in a nonvirulent form, which might affect their longevity and behavior.Deadly human diseases such as typhus, Rocky Mountain spotted fever, and Q fever are caused by Rickettsiae, obligate intracellular microorganisms associated with arthropod vectors (1). Wolbachia, a genus of the Rickettsial family, although not yet reported in mammals, is widespread among insects. More than a million insect species are estimated to contain the bacteria, which are maternally transmitted (2). Wolbachia are known, in various species, to cause cytoplasmic incompatibility (CI): crosses between bacteria-infected males and uninfected females produce few offspring, whereas infected females, due to an unknown mechanism, are resistant and produce ample progeny (3, 4). In the wasp, the bacteria can cause parthenogenesis: unfertilized eggs become diploid females instead of the usual haploid males (5). In the wood louse, Armadillidium vulgare, the bacteria feminize genetic males into functional females (6). These mechanisms provide advantages to the host in increasing progeny or accelerating evolution, while at the same time providing a venue for propagation of the host-dependent bacteria, which can grow in insect cells (7), but not in vitro. Therefore, the relationship between Wolbachia and host is generally regarded as symbiotic. Wolbachia can be transferred by injection, within or between species (8). Braig et al. (9) found that the bacteria from the mosquito Aedes albopictus, transferred by injection into uninfected embryos of Drosophila simulans, confer complete CI on the adults. The bacteria have been reported in a number of Drosophila species, associated with varied degrees of CI, including only weak or no effects (10-14). The various qualitative and quantitative effects seen in different Wolbachia-host combinations pose the question of what bacterium-host interactions are at play. Therefore it would be desirable to have a system for genetic analysis of these inte...