Tobacco smoking is probably the most important, controllable environmental risk factor in periodontitis. It results in changes in the vascular, inflammatory, immune and healing responses. The degree of exposure to tobacco smoking can be measured in pack years or by measuring serum cotinine and nicotine levels. In a previous paper we reported elevated levels of serum soluble intercellular adhesion molecule-1 (sICAM-1) in smokers, regardless of periodontal status. Elevated sICAM-1 has been found to be a risk marker for cardiovascular disease. In the present paper we report the short-term effects of an episode of smoking on blood flow and levels of sICAM-1. Human volunteers included non-smokers, light smokers and heavy smokers. Relative blood flow was monitored in the gingivae and forehead skin using a laser Doppler flowmeter and serum levels of sICAM-1, cotinine and nicotine measured before during and up to 60 min following an episode of smoking. We could not provide evidence to support the theory that there is localized vasoconstriction within the gingival tissues. In contrast, there was a significant increase in blood flow in the forehead skin of light smokers which was not observed in non-smoking controls or in heavy smokers, suggesting a long-term tolerance in this latter group. The level of sICAM-1 remained unchanged during this episode, further suggesting a long-term effect. In a parallel group of subjects, we were able to demonstrate a direct significant correlation between sICAM and serum cotinine levels. These observations may be relevant to aetiological mechanisms in periodontitis and other smoking-associated diseases.