The aim of this split-mouth-study was to compare the pharmacokinetic profile of two different doxycycline-gels (DOXY and ATRI) for topical subgingival application. Pharmacokinetics of both doxycycline-gels were analyzed in GCF and saliva. In 10 patients suffering from severe periodontitis, 10 pairs of contralateral defects were randomly assigned either to the first application of DOXY or ATRI. 14 days after the topical application of the first antibiotic gel, the application of the second gel in the contralateral defect took place. Clinical examinations at baseline showed no significant differences between sites treated with DOXY and ATRI. Samples of sulcus fluid and saliva were drawn baseline, 2, 5 and 24 hours after application, 2, 3, 4, 7, 9 and 11 days after application. Separation and quantitative measurement of both doxycycline-gels was performed with HPLC and UV-detection at 260 nm. In saliva specimens, time-dependent changes of mean doxycycline concentration were almost identical for both doxycycline-gels and declined from a maximum 2 hours after application (ATRI: 6653.90 ± 3096.14 ng/ml; DOXY: 5386.60 ± 1542.02 ng/ml [arithm. mean ± SEM]) to zero values 9 days after application. In crevicular fluid specimens, sites treated with ATRI exhibited a faster decrease of mean doxycycline concentration (1085.30, 264.00, 273.94, and 258.00 µg/ml measured 2, 5, 24, and 48 hrs. after application) than sites treated with DOXY (1388.38, 1300.40, 803.73, and 235.10 µg/ml). Both doxycycline-gels showed pharmacokinetics of controlled release delivery systems. Keywords: controlled release delivery, doxycycline, pharmacokinetics, topical application