Background The biological mechanisms underlying the association between psychological stress and hypertension are poorly understood. Increased plasma concentrations of the inflammatory proteins interleukin-6 and fibrinogen are commonly reported both in hypertensive patients and in people subject to chronic psychological stress. Recent laboratory studies have also shown that acute psychological stress increases plasma interleukin-6 and fibrinogen concentrations in healthy individuals. Objective To investigate the relationship between stress-induced inflammatory responses and blood pressure using a longitudinal design. Methods Participants were 153 individuals from the Whitehall 11 cohort. Blood pressure, plasma interleukin-6 and fibrinogen were assessed in response to an acute laboratory stressor, and ambulatory blood pressure was monitored on a separate day. Three years later, a follow-up day of ambulatory blood pressure monitoring was carried out. Results Individual differences in systolic pressure, fibrinogen and interleukin-6 stress responses predicted ambulatory blood pressure at the 3-year follow-up. Larger increases in ambulatory systolic pressure over the 3-year period were predicted by larger acute fibrinogen and interleukin-6 stress responses, independently of previous ambulatory blood pressure, acute blood pressure stress responses, age, sex, body mass and smoking. Conclusion Given the important roles of interleukin-6 and fibrinogen in hypertensive pathophysiology, these results indicate that psychological stress could promote hypertension through stimulating these inflammatory proteins. (c) 2005 Lippincott Williams & Wilkins.