The objectives of the present study were to establish in a long-term investigation the safety as well as the clinical and microbiological efficacy of scaling and rootplaning combined with local application of 2% minocycline hydrochloride-gel versus placebo-gel in patients with moderate to severe chronic adult periodontitis. This was an 18 months, randomized, double-blind, parallel, comparative study, in which 20 healthy patients with moderate to severe chronic periodontitis participated. At baseline, all patients received professional oral hygiene-instruction and supra- and subgingival scaling and root planing. The minocycline-gel was applied subgingivally baseline, 2 weeks, 1, 3, 6, 9 and 12 months. Microbiological evaluation was carried out using DMDx to identify the following bacteria: Porphyromonas gingivalis, Prevotella intermedia, Actinobacillus actinomycetemcomitans, Campylobacter rectus, Fusobacterium nucleatum and Treponema denticola. In addition standard microbiological techniques were used for the detection of P. gingivalis, P. intermedia, P. micros, A. actinomycetemcomitans, C. rectus, F. nucleatum, C. albicans and Enterobacteriaceae. Results showed a statistically significant improvement for all clinical parameters irrespective of the treatment modality. No differences were observed between test and control with regard to probing depth and attachment level. The DMDx data showed a significant reduction in both the numbers and the prevalence over the 15 months period, but no significant difference between groups. Culture data showed that at baseline two-third were positive for P. gingivalis and P. intermedia. Analysis over the 18 month period showed no significant difference between the two treatment modalities. C. albicans and Enterobacteriaceae were detected only in small proportions at each time interval in a limited number of patients. No adverse reactions were observed during the trial period. The present patient group responded favourably to scaling and rootplaning, but did not benefit from an effect of local of minocycline. Subgingival debridement in combination with oral hygiene instruction by itself has been shown to be effective. It remains to be studied whether local application of minocycline can be effective as an adjunct to mechanical therapy in sites that respond poorly to conventional treatment.