The present study was performed to assess and compare the clinical healing and the microbiological findings following local application of metronidazole or tetracycline to augment subgingival scaling in previously untreated adult periodontitis sites. Eighteen patients with moderate to severe adult periodontitis at single-rooted teeth were selected. In each patient, 3 interproximal sites having comparable root anatomy, probing depth > or =5 mm and bleeding on probing were randomly assigned to 1 of 3 treatment groups: 1) two sessions of subgingival scaling and root planing; 2) similar to 1, with each treatment supplemented with a 25% metronidazole sustained release gel; 3) similar to 1 with each treatment supplemented with a 3% tetracycline ointment. The treatments were performed by 1 operator and the clinical variables probing depth, attachment level, and bleeding on probing were evaluated at baseline, 3 months and 6 months by a second blinded examiner. The microbiological findings were evaluated using a commercial test kit. The average probing depth reduction for the 3 groups at 6 months was 1.5 mm and the average gain of clinical attachment was 0.8 mm. There were no significant differences between the effects following topical application of the metronidazole gel or the tetracycline ointment. Scaling and root planing alone appeared as effective as the drug augmented regimens, although there was a weak but non-significant tendency for better results in sites treated with the antibiotic drugs. Actinobacillus actinomycetemcomitans was generally not detected; Prevotella intermedia was not significantly reduced, while Porphyromonas gingivalis was significantly reduced in all treatment groups. It was concluded that the augmentative effect of the metronidazole gel and the tetracycline ointment was comparable but small compared to scaling and root planing alone. The clinical importance of such small augmentation effects should be further evaluated.