The purpose of the present study was to assess the relation between clinical parameters and concentrations of the key (IL-1beta, TNF-alpha, IL-2, IFN-gamma, IL-4, IL-10) cytokines, important in the initiation and progression of periodontal diseases, within inflamed gingival tissues and serum samples from patients with severe chronic periodontitis. Twenty-five patients with severe chronic periodontitis, who had sites with probing depths (PD) > 5 mm, and 25 periodontally healthy persons were included in the study. Clinical examinations including PD, clinical attachment loss, plaque index, and bleeding index were performed before periodontal treatment. Gingival tissue biopsies were collected from one active site of each patient and from healthy individuals, and blood samples were withdrawn on the day of tissue biopsy. The concentrations of cytokines were determined by an enzyme-linked immunosorbent assay, and the relationship between their profiles in situ and in circulation with clinical parameters was analysed. The concentrations of IL-1beta, TNF-alpha, IL-2, IFN-gamma were, on average, significantly higher in serum samples and gingival tissue biopsies from periodontitis patients than in healthy controls. However, serum samples from both groups showed high individual variability of cytokine profiles, and no association between cytokine concentrations and clinical parameters of periodontitis was found. On the contrary, the levels of IL-4 and IL-10 in both kinds of samples obtained from patients and controls were generally low or even undetectable, and remained, on average, on the same level. However, the frequency of IL-4 (88% positive samples) and IL-10 (72%) was much higher in healthy gingival tissues. High concentrations of TNF-alpha, IFN-gamma and IL-2 and, especially, a high ratio of IL-1beta/IL-10 and TNF-alpha/IL-4 found in tissue biopsies from periodontitis patients, strongly correlated with the severity of periodontitis. These results indicate that high variability of cytokine concentrations and low frequency of their detection in serum samples from periodontitis patients make these determinations useless for the detection of disease presence and/or its severity. In contrast, high absolute levels of IL-1beta, TNF-alpha, IL-2 and IFN-gamma and, especially their high ratios to IL-4 and IL-10 found in inflamed tissue biopsies, were closely associated with periodontal disease severity.