Current advances in the understanding of the pathogenicity of the agents of diarrheal infections, Vibrio cholerae, diarrheagenic E. coli, Shigella, Salmonella, and enteropathogenic Yersinia, have, to a great extent, become possible due to morphological studies of host-pathogen interactions in natural and experimental infections. Despite a multigenic nature and a diversity of pathogenic features in the bacterial species and even in serogroups of the same species, it is now possible to delineate four major patterns of interaction of enteric pathogens with their cellular targets, the enterocytes, and with the immune apparatus of the gut. These patterns, epicellular cytotonic, epicellular restructuring cytotonic, invasive intraepithelial cytotonic and cytotoxic, and invasive transcellular cytotonic and cytotoxic bacteremic, underlie early pathogenesis and clinical manifestations in the respective diarrheal diseases. In this review, the results of the morphological analyses of these patterns over the last 3 decades as well as some methodological problems encountered in the interpretation of morphological observations are discussed.