Because cigarette smoking is a definite risk for the development of cardiovascular disease and nicotine induced vasoconstriction may be a possible pathogenetic factor the haemodynamic effects of smoking cigarettes with high or low nicotine content were compared with those induced by chewing nicotine gum in a placebo controlled, crossover study in six healthy volunteers. The three stimuli induced similar increases in heart rate (about 20%) and systolic blood pressure (about 7%) and a decrease in digital blood flow. Although the mean haemodynamic changes parallelled the mean plasma nicotine concentration increases, no correlation was found between them when the individual values were considered. It is concluded that the nicotine induced haemodynamic changes probably occur as a result of the (local) release of vasoactive mediators such as adrenaline or noradrenaline after a threshold plasma nicotine concentration has been reached. Such a threshold may explain the large interindividual variability in susceptibility to smoking induced cardiovascular diseases. blood with a possible decrease of the oxygen supply to the endothelial cell.' In the present study, we compared the haemodynamic response of young healthy smokers to three different nicotine stimuli: a cigarette with high or low nicotine content and a nicotine chewing gum. These three stimuli were compared with a placebo in a crossover study,8 and the induced haemodynamic changes were correlated with increases in the plasma nicotine concentration. Subjects and methods STUDY PROTOCOLSix healthy male smokers (mean(SD) age 30(2.8) years; mean(SD) cigarette consumption 8.2 (1.1) pack year, where 1 pack year corresponds to smoking 1 pack of 20 cigarettes per day during one year) were enrolled in a crossover, placebo controlled study. The trial was carried out according to the Declaration of Helsinki and was approved by the human ethical committee of our institution. The study consisted of 154