AIM: Transient bacteraemia and endotoxaemia, and elevated levels of systemic cytokines have been reported following subgingival debridement. This study aimed to investigate the effect of chlorhexidine (CHX) solution on circulating levels of lipopolysaccharide (LPS) and interleukin-6 (IL-6) when used as an irrigant during ultrasonic debridement in patients with periodontitis. MATERIAL AND METHODS: Eighteen patients with moderate to advanced chronic periodontitis were treated in a split-mouth, crossover, single-masked study. Irrigation with 0.02% CHX solution or water was used during treatment of two ipsilateral quadrants on two separate occasions 7 days apart, randomized as to order. Peripheral blood samples were collected for circulating levels of LPS and IL-6 at baseline, 5 and 120 min. after instrumentation commenced. RESULTS: Median concentrations of LPS were elevated from baseline to 5 min. into treatment with both CHX and control irrigant (p<0.05). Median levels of IL-6 increased with both treatments from baseline to 120 min. (p<0.001): CHX, 0.81-1.85 pg/ml; control, 0.78-1.78 EU/ml. CONCLUSIONS: Ultrasonic instrumentation in patients with moderate to advanced periodontitis increases circulating levels of LPS after 5 min. and IL-6 120 min. after commencement of treatment, and is not affected by using 0.02% CHX as an irrigant instead of water.