Refractory periodontitis manifest progressive attachment loss in a rapid and unrelenting manner regardless of the type or frequency of therapy applied. The purpose of this study was ta evaluate the relation between the level of cytokines in GCF and periodontopathic microflora with disease activity of refractory periodontitis. Selection of patients with refractory periodontitis (7 males, 3 females) were made by long term clinical observation including conventional clinical history and parameters. Teeth that showed pocket depth greater than 6mm were selected as sample teeth. Subjects were examined at baseline and after 3 months. Prior to baseline test, individual acrylic stent was fabricated. Reference grooves were made on each sample tooth site. Pocket depth and attachment loss were measured by Florida Probe. Gingival index was measured at 4 sites each sample teeth. Disease activity was defined as attachment loss of ${ge}$ 2.1mm, as determined by sequential probing and tolerance method. The pattern and amount of alveolar bone resorption was observed with quantitative digital subtraction image processing radiography. Morphological analysis of subgingival bacteria was taken by phase contrast microscopy. Predominant cultivable bacterial distribution and frequency were compared between disease-active and disease-inactive site using immunofluorescence microscopy and selective microbial culturing. Levels of $interleukin-l{eta}$, 2, 4, 6 and $TNF-{alpha}$ in GCF and blood serum sample were quantified by ELISA. In active sites, P. intermedia was significantly increased to compare with inactive site. $IL-1{eta}$, IL-2, IL-6 and $TNF-{alpha}$ in GCF were increased in active sites and IL-2 in serum was increased in active patients significantly. Alveolar bone loss in active site was correlated with $IL-1{eta}$, IL-2 in GCF. And loss of attachment in active site was correlated with IL-2 in GCF. These results demonstrate that IL-2 in serum, $IL-1{eta}$, IL-2, IL-6 and $TNF-{alpha}$ in GCF, P, intermedia might be used as possible predictors of disease activity in refractory periodontitis before it is clinically expressed as attachment loss and quantitative alveolar bone change.