In this study 17 strains of Porphyromonas gingivalis, both reference and clinical isolates, were investigated for their in vitro interaction with human polymorphonuclear leukocytes, hydrophobicity, density, and virulence in a mouse model. The results of the phagocytosis, hydrophobicity, and density experiments showed that P. gingivalis strains could be divided into two distinct groups. One group of strains were readily attached and phagocytosed when exposed to the leukocytes. These bacteria were hydrophobic and had a higher buoyant density than the other group, which were poorly phagocytosed, had a low buoyant density, and were hydrophilic. This latter group also exhibited an extracellular meshwork resembling a glycocalyx when examined by electron microscopy. There were also significant differences between strains in the mouse pathogenicity model. Two strains caused an invasive, spreading infection compared with the other 15 strains which produced small, localized abscesses. There was no clear correlation between the results of the phagocytosis assay and the virulence of the bacteria when injected subcutaneously in mice. Resistance to phagocytosis may be important for survival of these bacteria, but it does not in itself imply the ability to cause damage to the host.