The purpose of this study was to evaluate the safety and clinical efficacy of controlled-release tetracycline-containing fibers in patients with refractory periodontitis versus the preceding classical treatment. One hundred twenty-one sites in 20 patients were followed from baseline to 6 months after fiber insertion. Each selected site was > or = 5 mm deep and bled on probing. All 20 patients had at least one site > or = 7 mm which bled on probing. Those pockets remained after intense and repeated conventional therapy (scaling and root planing and often surgery), often including the use of systemic antibiotics. This treatment period, the so-called control period, preceded the experimental period by at least 3 years, when the fibers were placed. Both treatments (in control and test period) were performed in the Department of Periodontology at the University Hospital in Leuven. At the start of the experimental period, all pockets > or = 5 mm were treated by the placement of fibers impregnated with 25% tetracycline. The fibers were removed after 10 days. Probing depth, clinical attachment level, gingival recession, and bleeding on probing were recorded at baseline, and at 1, 3, and 6 months following treatment. Analysis of data from all sites indicated that a significant decrease in probing depth and gain in attachment were present at all follow-up visits. The mean probing depth reduction for sites > or = 7 mm was 3.2 mm at month 6, with a gain in attachment of 2.7 mm, while this was -1.0 mm and -1.9 mm, respectively, during the preceding control period. The fraction of bleeding pockets was reduced from 77% to 27% and from 80% to 77% during the experimental and control periods, respectively. No significant adverse side-effects were observed, except for a transient redness at fiber removal in 2 sites. Fiber insertion appeared to be time-consuming even when the operator was familiarized with the procedure. The results of this study prove that tetracycline-impregnated fibers can reduce probing depth significantly for a period of 6 months in patients not responding to thorough and repeated classical periodontal treatment.