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When infecting a human host, <i>Corynebacterium diphtheriae</i> and <i>Corynebacterium ulcerans</i> are able to impair macrophage maturation and induce cell death. However, the underlying molecular mechanisms are not well understood. As a framework for this project, a combination of fluorescence microscopy, cytotoxicity assays, live cell imaging, and fluorescence-activated cell sorting was applied to understand the pathogenicity of two <i>Corynebacterium</i> strains isolated from fatal cases of systemic infections. The results showed a clear cytotoxic effect of the bacteria. The observed survival of the pathogens in macrophages and, subsequent, necrotic lysis of cells may be mechanisms explaining dissemination of <i>C. diphtheriae</i> and <i>C. ulcerans</i> to distant organs in the body.