Respiratory tract infections may acutely increase risk from coronary heart disease (CHD), though the mechanisms have not been defined. Patients with chronic obstructive pulmonary disease (COPD) are prone to repeated exacerbations that are often associated with respiratory infections. These patients also have increased cardiovascular morbidity and mortality. We hypothesized that transient acute increases in plasma fibrinogen, an independent risk factor for CHD, could occur at COPD exacerbation (mediated through a rise in IL6) and thereby provide a mechanism linking respiratory infection to risk of coronary heart disease. 93 COPD patients [mean (SD) age 66.8 (8.1) years] were followed regularly over one year, with daily diary card monitoring of respiratory symptoms and peak expiratory flow rate (PEFR); 67 patients [mean FEV1 1.06 (0.44) l, FVC 2.43 (0.79) l] were seen during 120 exacerbations. At each visit spirometry was measured and blood samples taken for plasma fibrinogen and Interleukin-6 (IL-6) levels. At baseline, the mean (SD) plasma fibrinogen was elevated at 3.9 (0.67) g/l in the 67 patients with exacerbations during the study and the median (IQR) IL-6 at 4.3 (2.4 to 6.8) pg/ml. Plasma fibrinogen increased by 0.36 (0.74) g/l at exacerbation (p <0.001). with IL-6 levels rising by 1.10 (-2.73 to 6.95) pg/ml (p = 0.008). There was a relation between the changes in fibrinogen at exacerbation and IL-6 levels (r = 0.348, p <0.001). Multiple regression revealed significantly greater rises in fibrinogen when exacerbations were associated with purulent sputum (b = 0.34 g/l; p = 0.03), increased cough (b = 0.31 g/l, p = 0.019) and symptomatic colds (b = 0.228; p = 0.024). Plasma fibrinogen levels were elevated in stable patients with COPD and may contribute to the increased cardiovascular morbidity and mortality in these patients. COPD exacerbations increased serum IL-6 levels, leading to a rise in plasma fibrinogen. Thus acute rather than chronic infection may have a role in predisposing to coronary heart disease or stroke.