It is becoming increasingly apparent that periodontitis consists of mixture of diseases, most of which respond favorably to traditional mechanical therapy. Among these variants of the disease, some appear to be associated with unusual microbial infections and defective host defenses. Many of these fail to respond to conventional treatment. The recognition that some forms of periodontitis are refractory to standard periodontal therapy has given rise to a new classification of peridontitis. A series of 1692 subgingival microbial samples sent to a diagnostic microbiology laboratory included 738 samples that could be identified as compatible with a clinical diagnosis of refractory or recurrent periodontitis. In descending order of prevalence the associated microbiota included Bacteroides forsythus(85%) ,Fusobacterium species(78%), Spirochetes(67%), Campylobacter rectus(64%), Porphyromonas gingivalis(59%), Peptostreptococcus micros(58%), motile rods(46%), Prevotella intermedia(33%), Eikenella corrodens(13%), Capnocytophaga species(12%) ,and Actinobacillus actinomycetemcomitans(6%). Antibiotic resistance to tetracycline, penicillin G, or metronidazole was particularly noticeable for Fusobacterium species, Capnocytophaga species, and Actinobacillus actinomycetemcomitans. It was largely absent for Campylobacter rectus. No antibiotic data were obtained for Porphyromonas gingivalis or Bacteroides forsythus, as these species were detected by immunofluorescence. The results indicate that a substantial number of microorganisms associated with refractory periodontitis are variably resistant to commonly-used antibiotics. Diagnostic microbiology must be considered an essential adjunct to the therapist faced with periodontal lesions refractory to conventional treatment.