Eikenella corrodens is a gram-negative facultative bacillus commonly found in the oral cavity. Although the role of E. corrodens in periodonititis is not clear, its isolation from extraoral infections attests to its pathogenic potential. Previous studies suggested that this species is phenotypically diverse. In the present study, we used restriction endonuclease analysis (REA) to assess the genetic diversity of this species and to explore the applicability of REA in studying the transmission of E. corrodens. Two groups of E. corrodens isolates were used in this study. Group 1 included 47 epidemiologically independent isolates recovered from dental plaques in periodontally healthy subjects and periodontitis patients and from extraoral infections in different geographic areas. Group 2 E. corrodens included 40 isolates recovered from two periodontitis patients and two periodontally healthy subjects. The results indicated that E. corrodens is genetically heterogeneous, as determined by REA. The majority of the group 1 E. corrodens isolates exhibited strain-specific restriction patterns. Forty restriction patterns were distinguishable among the 47 isolates. Analyses of group 2 isolates revealed that three of four subjects harbored more than one clonal type of E. corrodens. In one instance, a periodontitis patient was found to be colonized by six different clones. Furthermore, two different clonal types of E. corrodens were recovered from a single periodontal pocket in this patient. The results indicated that REA may be a useful tool in the epidemiologic investigation of E. corrodens infections.