This study investigated the bacterial diversity in human subgingival plaque using culture-independent molecular methods to obtain full 16S rRNA sequences for all cultivable and non-cultivable oral bacteria. Subgingival plaque samples were collected from healthy individuals and those with various periodontal diseases, including refractory periodontitis, adult periodontitis, HIV periodontitis, and acute necrotizing ulcerative gingivitis. A total of 2,522 clones were analyzed, with approximately 60% falling into 132 known species and 40% representing novel phylotypes. Of the 215 novel phylotypes, 75 were identified in multiple subjects. Known periodontal pathogens such as Porphyromonas gingivalis, Bacteroides forsythus, and Treponema denticola were identified, but typically as minor components of the plaque. Several phylotypes were found in extreme natural environments where no cultivable species are known. Some species or phylotypes were found only in diseased subjects, while others were found only in healthy subjects. The study estimated that there are 415 species in subgingival plaque, with 68 additional unseen species. When considering other oral surfaces, the total species diversity in the oral cavity is estimated to be approximately 500 species. The study highlights the importance of understanding the oral microbiome for diagnosing and treating both oral and systemic diseases. The results suggest that many oral bacteria are not cultivable with current methods, and further research is needed to identify and characterize these novel phylotypes. The study also emphasizes the need for molecular techniques to explore microbial diversity in the oral cavity.This study investigated the bacterial diversity in human subgingival plaque using culture-independent molecular methods to obtain full 16S rRNA sequences for all cultivable and non-cultivable oral bacteria. Subgingival plaque samples were collected from healthy individuals and those with various periodontal diseases, including refractory periodontitis, adult periodontitis, HIV periodontitis, and acute necrotizing ulcerative gingivitis. A total of 2,522 clones were analyzed, with approximately 60% falling into 132 known species and 40% representing novel phylotypes. Of the 215 novel phylotypes, 75 were identified in multiple subjects. Known periodontal pathogens such as Porphyromonas gingivalis, Bacteroides forsythus, and Treponema denticola were identified, but typically as minor components of the plaque. Several phylotypes were found in extreme natural environments where no cultivable species are known. Some species or phylotypes were found only in diseased subjects, while others were found only in healthy subjects. The study estimated that there are 415 species in subgingival plaque, with 68 additional unseen species. When considering other oral surfaces, the total species diversity in the oral cavity is estimated to be approximately 500 species. The study highlights the importance of understanding the oral microbiome for diagnosing and treating both oral and systemic diseases. The results suggest that many oral bacteria are not cultivable with current methods, and further research is needed to identify and characterize these novel phylotypes. The study also emphasizes the need for molecular techniques to explore microbial diversity in the oral cavity.