Aims Thrombin is an important factor in the pathogenesis of thrombotic diseases. To clarify whether smoking has an effect in platelet-dependent thrombogenesis, we studied the acute effects of smoking on platelet-dependent thrombin level in smokers. Methods and Results Subjects consisted of ten smokers and nine non-smokers. Platelet-dependent thrombin level measured after overnight fasting was greater in smokers than in non-smokers (smokers vs non-smokers, 121 +/- 47 vs 56 +/- 5 mIU. ml(-1), P<0.01). When subjects in the smokers group smoked two cigarettes containing 0.9 mg of nicotine per cigarette, platelet-dependent thrombin levels showed a transient three-fold increase in blood samples obtained immediately after smoking (365+/-76mIU.ml(-1), P< 0.001). Thrombin levels in the blood samples obtained 10 min and 30 min after smoking were less than that in the samples obtained immediately after smoking ceased, but were not significantly different from those in the samples obtained before smoking. Blood nicotine level increased significantly immediately after smoking (P<0.001), and plasma protein C activity decreased significantly 30 min after smoking (P<0.05). When nicotine or cotinine was added to the platelet-rich plasma of non-smokers ex vivo, the platelet-dependent thrombin level increased significantly (P<0.002). Conclusion Platelet-dependent thrombin level is enhanced in smokers, even when not smoking, when compared with non-smokers and increases immediately after smoking. Increases in nicotine and cotinine levels caused by smoking induced a prothrombotic state in smokers via increased platelet-dependent thrombogenesis. (Eur Heart J 2001; 22: 5-61, doi:10.1053/euhj.1999.1938) (C) 2001 The European Society of Cardiology.