The aim of this study was to evaluate the efficacy of 3 commercially available periodontal systems for local delivery of antibiotics as adjuncts to scaling and root planing in treatment of sites with persistent periodontal lesions following a course of scaling and root planing. Fifty-four patients with 4 pockets > or = 5 mm and bleeding on probing and/or suppuration were randomized in 4 treatment groups including: scaling and root planing plus application of 25% tetracycline fiber (S + Tet) (13 patients), scaling and root planing plus application of 2% minocycline gel (S + Min) (14 patients), scaling and root planing plus application of 25% metronidazole gel (S + Met) (14 patients), and scaling and root planing alone (S) (13 patients). Clinical measurements were taken at baseline and 6 weeks after the end of treatment periods. All treatments were applied using the distributors' recommended protocols and resulted in significant improvement in probing depth, attachment level, bleeding on probing and the modified gingival index (MGI) scores. The improvements in clinical parameters were greater in all three adjunctive treatment groups than scaling and root planing alone. The mean probing depth reductions were: S + Tet = 1.35 mm, S + Met = 0.95 mm, S + Min = 0.87 mm and S = 0.60 mm. The probing depth reduction was significantly greater in the scaling plus tetracycline fiber group than the scaling and root planing alone group (P = 0.002). The difference between groups in improvement of attachment level or bleeding on probing was not significant Scaling plus tetracycline fiber treatment resulted in the greatest reduction in the MGI scores which was significantly greater than all other groups. While the frequency of sites with suppuration was markedly reduced following all treatments, it reached zero in the scaling plus tetracycline fiber group. No serious adverse effects were observed or reported for any treatment. While all three locally applied antimicrobial systems seem to offer some benefit over scaling and root planing alone, a treatment regimen of scaling and root planing plus tetracycline fiber replacement gave the greatest advantage in the treatment of persistent periodontal lesions at least during the 6-week period following treatment.