Soluble adhesion molecules have been reported as risk markers of a wide range of human diseases and specific adhesion molecules may play a direct role in pathological processes. Serum soluble intercellular adhesion molecule-1 (sICAM-1) is known to be significantly elevated in smokers compared to non-smokers. We examined the acute effects of smoking a standard 2R1 research cigarette on the serum concentration of sICAM-1 and other circulating adhesion molecules (sP-selectin, sE-selectin, sL-selectin, sVCAM-1 and sPECAM-1) in heavy smokers (serum cotinine ≥ 100 ng/ml), light smokers (serum cotinine ≤ 60 ng/ml) and non-smokers (serum cotinine ≤ 10 ng/ml) by ELISA. Adhesion molecule expression on the cell surface of monocytes and neutrophils in peripheral blood was examined by flow cytometry. The sICAM-1 concentration directly correlated to serum cotinine concentration (p= 0.047) and nicotine load (p= 0.033) in smokers and was significantly elevated compared to non-smokers (p= 0.037). Other than a decrease in the concentration of sP-selectin over 1 hour regardless of smoking, no significant temporal alterations of any adhesion molecule were observed following the smoking experience or in the non-smoking control group. No significant difference in surface expression of ICAM-1, CD18, PECAM-1 or L-selectin on peripheral monocytes or neutrophils was observed over a 1-hour period following smoking. These data suggest that the elevated concentration of sICAM-1 in smokers is not due to an immediate effect of smoking.