This investigation was conducted on seven individuals referred for treatment of moderate adult periodontitis. Twenty-eight sites with an average probing depth of 5.6 +/- 0.9 mm were evaluated. One tooth per jaw quadrant was randomly assigned to receive one of the following treatments: (I) no treatment, i.e., control; (II) saline irrigation; (III) tetracycline irrigation and (IV) scaling and root planing (SC/RP). A plaque control program was instituted one week prior to the experimental period and reinforced throughout the eight-week study. Irrigation was performed every 48 hours during the first two weeks of the experiment for Groups II and III, and the single treatment of SC/RP was carried out immediately following the baseline examination for Group IV. Clinical and microbiologic changes were monitored every two weeks using plaque and gingival indices, gingival fluid flow, probing depths, bleeding on probing and dark-field microscopic examination of the subgingival microbial flora. The tetracycline and SC/RP treatment modalities resulted in statistically significant clinical and microbiological improvements when compared with the control. Tetracycline irrigation alone and SC/RP alone had a similar effect in changing the subgingival microflora from one associated with disease to one associated with health. Thus, these treatment modalities are effective methods of producing statistically significant alterations in the subgingival microflora. The property of substantivity may contribute to the sustained duration of the effect of locally delivered tetracycline.