Objective: Smoking is an important environmental risk factor for the initiation and progression of periodontal diseases. The aim of this study was to evaluate the effects of smoking on clinical parameters and the gingival crevicular fluid (GCF) contents of the pro-inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels in patients with chronic periodontitis. Material and Methods: The study base consisted of 41 patients including 22 volunteer current smokers with an age range of 32-59 (44.41 ± 7.88) years and 19 volunteer non-smokers with an age range of 36-59 (46.94 ± 6.07) years. The first month after non-surgical periodontal therapy was accepted as the baseline of the study. The clinical parameters including plaque index (PI), gingival index (GI), bleeding on probing (BOP), probing depth (PD), clinical attachment loss (CAL) were recorded and GCF samples were collected for analysis of GCF contents of DL-6 and TNF-α levels. At the 3rd and 6th months, all of these procedures were repeated. Results: In smokers, only CAL was significantly higher at the 3rd month compared with non-smokers (p < 0.05). GI and BOP were higher in non-smokers than smokers in both periods (p < 0.05). PI showed increases from the initial to the 6th month in smokers (p < 0.05). Although the differences between two groups with regard to EL-6 and TNF-α were not significant (p > 0.05), the total amount of TNF-α in GCF decreased from the initial to the 6th month in smokers (p < 0.05). There were no significant correlations between the mean total amount of IL-6 and TNF-α in GCF and clinical parameters in both evaluation periods in smokers (p > 0.05). Conclusion: The present study demonstrated that cigarette smoking increases the amount of dental plaque over time in smokers and does not influence GCF contents of IL-6 and TNF-α. © Blackwell Munksgaard, 2004.