Invasion of gingival and junctional epithelial cells has been recently proposed as a potentially relevant mechanism in the pathogenesis and recurrence of periodontal disease. The gram negative anaerobe Prevotella nigrescens was shown to be involved in the development of periodontal lesions in man, suggesting a possible involvement of invasivity as a mean to circumvent the host immune surveillance and other hostile factors. Appropriately designed invasion assays demonstrated that P. nigrescens efficiently invades human epithelial cells, through a mechanism whose efficiency is influenced by the phase of growth, by the multiplicity of infection, and by the cell line used, and that requires microfilament integrity, but is not affected by an impairment of microtubule organization. Intracellular replication assays suggested that P. nigrescens probably multiplies within Kb epithelial cells, causing extensive cell alterations. Invasion of gingival epithelial cells could consequently be a basic step in the virulence mechanism of the species.