Nicotine-induced expression of P-selectin is implicated in endothelial cell damage related to smoking. Thirty male Sprague-Dawley rats were divided into three groups: two experimental and one control. Both experimental groups were exposed to cigarette smoke for four weeks, but one group was also given anti-P-selectin antibody (100 microg IgG per 100 g body weight) intravenously. Rolling and adhesion leucocytes within the microcirculation of the cremaster muscle were measured. The urine cotinine concentrations of rats exposed to smoke were 612 ng/ml higher than those of non-smokers. Both rolling and adherent leucocytes were highest and steady in the group given anti-P-selectin antibody at about 50 and 10, respectively. There was a significant drop in both rolling and adherent leucocytes (31 to 4 and 5 to 2) after the anti-P-selectin antibody had been given. However, this effect was short-lived as both increased above those at 35 minutes by 120 minutes (p<0.001). The increase in leucocyte rolling and adherence caused by smoking can be lowered by giving anti-P-selectin antibody. The effective period in rats was two hours, with the maximal effect one hour after injection.