Cytoplasmic incompatibility (CI) is a unique form of male sterility found in numerous insect species that harbor a bacterial endosymbiont Wolbachia. CI is characterized by severe reduction in the progeny produced when infected males are crossed to uninfected females. The reduction in progeny correlates with developmental defects that arise during and immediately following fertilization, suggesting that sperm function is disrupted. To investigate the nature of the cellular defects associated with CI, fertilization and early embryonic development were examined in normal and incompatible crosses of Drosophila simulans using anti-sperm, anti-tubulin and anti-chromatin antibodies. Although pleiotropic, defects associated with CI can be classified into five broad categories: (1) sperm defects in the egg; (2) aberrant morphology of the mitotic apparatus; (3) defects in chromatin structure; (4) proliferation of centrosomes in the absence of nuclear division; and (5) loss of mitotic synchrony. Although mitosis and chromosome behavior are severely disrupted in CI crosses during early development, centrosome duplication and migration appear to continue unabated. The available cytological data suggest that the primary defects observed in incompatible crosses are due to defects in chromosome replication/segregation and in associated centrosome/microtubule-based processes.