Samples of subgingival plaque were collected from periodontal patients receiving two different tetracycline treatment regimens following conventional periodontal therapy. Four patients had received an oral dose of 1000 mg/day for 2 weeks and nine had received 1000 mg/day for 1 week followed by 250 mg/day for extended time periods. The latter regimen is similar so that commonly prescribed for the chronic skin disease, acne vulgaris. Taxonomic characterization of plaque isolates indicated that the predominant organisms cultured from both treatment groups were species of Streptococcus and the branching, filamentous Gram-positive rods, Actinomyces and Rothia. A much greater microbial complexity was observed among the flora isolated from patients taking 250 mg/day. The latter group harbored many of the fastidious Gram-negative organisms presently implicated in the etiology of periodontal disease. All bacterial strains isolated were tested for resistance to tetracycline by replica-plating cultures on an agar medium containing two-fold dilutions of the antibiotic. Streptococcus, Veillonella and Neisseria were the bacterial genera found to be consistently resistant to tetracycline, with minimum inhibitory concentrations as high as 128 micrograms/ml. Among the Actinomyces, selection for antibiotic resistance was common only within a single species, A. odontolyticus. However, A viscosus strains isolated at 54% of the subgingival flora from one patient did demonstrate an intermediate resistance level, growing on concentrations up to 8 micrograms/ml. Tetracycline resistance was shown by a variety of Gram-negative rods isolated from the low dosage group. Although a minimum number of patients were studied, extensive microbial analyses of the predominating subgingival bacteria indicated that the goal of tetracycline therapy was achieved during the 2-week therapy period at 1000 mg/day.