In the present study we examined alterations in the proportions of cultivable flora of A. actinomycetemcomitans (A.a.) in subgingival plaque of 25 patients with different forms of periodontitis, 7 days after systemic administration of 200 mg/d Minocycline-HCl. Remarkable shifts in the flora were apparent. Sites with low or extremely low initial levels of A.a. (less than 10%) showed an increase in mean proportions from 2.7% to 15.7% (p less than 0.01). A.a. was eliminated in only 18% of sites after 1 week of minocycline therapy. Subgingival scaling resulted in 80% of sites without detectable A.a. However, if present, the organism accounted for 51% of the cultivable microflora, on average. Our data emphasize the importance of a sufficiently extended period of antibiotic therapy and efficient mechanical debridement of all tooth surfaces to eliminate the organism.