THE PURPOSE OF THIS STUDY was to investigate the distribution of several periodontopathic bacteria in adult periodontitis, their in vitro susceptibility to minocycline-HCl, and whether the efficacy of the drug changes with a decrease in bacterial susceptibility. Twenty-one patients (43 to 75 years old) with 62 periodontal lesions from pockets greater than or equal to 4 mm participated in the study. After subgingival sampling, an ointment containing 2% minocycline-HCl was applied locally to the selected pockets once a week for 4 weeks. The lesions were clinically examined after 1 and 4 weeks of administration. The distribution of the subgingival microorganisms included Capnocytophaga sputigena (37.1%), Prevorella intermedia (22.6%), Porphyromonas gingivalis (22.6%), Fusobacterium nucleatum (20.1%), Actinobacillus actinomycetemcomitans (9.7%), and Eikenella corrodens (4.8%). The distribution was complex, with 76.8% of the sites containing 1 to 3 bacterial spieces. The minimum inhibitory concentration (MIG) of minocycline-HCl for each organism showed that most were inhibited by a minocycline-HCl concentration equal to or less than the MIC for reference strains. However, some clinical strains of Prevotella intermedia seemed to exihibit low susceptibility to minocycline-HCl. There were no significant differences among sites with strains exhibiting low or normal susceptibility to minocycline-HCl. The concentration of the drug applied to deep periodontal pockets inhibited the growth of most of the microorganisms investigated in this study.