Data from the Whitehall II Study and others have demonstrated a role for the metabolic syndrome and fibrinogen underlying the association between social position and coronary heart disease. In this study, we examined the role of an additional hemostatic factor and marker of endothelial dysfunction, von Willebrand factor (vWF). Four thousand five hundred and forty-eight men and 1837 women were examined in the third phase of the study, which took place between 1991 and 1993. Employment grade was used as a measure of socioeconomic position. An inverse relation between employment grade and vWF was evident (P<0.0003). This employment grade gradient was apparent overall, and the relation persisted even when nonsmokers and participants with poor health were removed from the analyses (P=0.02). The difference between the highest (unified grades 1 to 6) and lowest (clerical/support) employment grades in vWF concentrations was 8.9 IU/dL (95% CI 6.0, 11.8; P<0.001) for men and 6.9 IU/dL (95% CI 4.0, 9.7; P=0.06) for women. vWF was associated with a number of biological factors that themselves showed an employment grade gradient, including fibrinogen (P<0.001), fasting and postload glucose (P<0.05) levels, and fasting and postload insulin (P<0.01) levels. Associations with smoking and alcohol intake were apparent. Smoking showed a threshold effect, such that only men who smoked >21 cigarettes per day produced a significantly increased vWF level (P<0.05) compared with lighter smokers. The health-related behaviors explained 25% of the grade gradient in men and 28% in women, while the biological factors accounted for 32% in men and 22% in women. We conclude that there is a grade gradient in vWF that was not fully explained by health-related behaviors and risk factors for coronary heart disease. These data are consistent with the hypothesis that endothelial dysfunction is part of the explanation for social inequalities in cardiovascular disease.