The in vitro inhibitory effect of several antimicrobial agents was determined against dispensed dental plaque samples taken from periodontally diseased sites as an aid in the selection of antibiotics for adjunctive use in periodontal therapy. 2 groups of patients were sampled. 1 group of 10 patients with severely advanced disease had received periodontal treatment which included the frequent adjunctive use of an antibiotic. The second group consisted of 15 individuals with less severe periodontal disease; only 4 individuals had been previously treated with antibiotics for their periodontal disease. Bacterial samples of subgingival plaque were taken from each patient and tested against a battery of antibiotics to determine which agent was the most effective in suppressing bacterial growth. Each antibiotic was incorporated into Trypticase-soy blood agar at a concentration equivalent to that achieved in either gingival fluid or blood following recommended oral dosages. The inhibitory effect was determined by comparing the number of bacterial recovered on the antibiotic-containing medium to the total number of bacteria recovered on the basal medium. Penicillins, with the exception of cloxacillin, were the most effective in inhibiting bacterial growth. Benzylpenicillin consistently inhibited the growth of 90% of the isolates recovered on media free of antibiotics while ampicillin and amoxicillin frequently inhibited 99% or more of the bacteria recovered. Tetracycline was generally inhibitory for at least 90% of the isolates if the patients had not been previously treated with this agent. However, resistance to this drug was common in samples taken from patients previously treated with tetracycline. Doxycycline, a tetracycline derivative, did not inhibit significantly more isolates than tetracycline. Clindamycin was inhibitory for 90% or more of the organisms in most of the samples; and, was usually effective in inhibiting isolates in samples which exhibited large numbers of isolates resistant to tetracycline. Erythromycin was relatively ineffective against the isolates recovered from samples from the severely diseased group but was inhibitory to isolates in some samples taken from the more moderately diseased group. Metronidazole, at the concentration tested, was largely ineffective against the isolates in bacterial samples from both groups. No single antimicrobial agent was found to be inhibitory for greater than 90% of the bacteria recovered from all of the subgingival plaque samples with the possible exception of some penicillins.