Fibrinogen may play an active role in the development and progression of atherosclerotic plaques. We assessed the association between fibrinogen levels and atherosclerotic plaques over three different arterial sites in an asymptomatic never-treated male population with increased cardiovascular risk. We included 652 men aged 40 to 60 years old with at least one of the following cardiovascular risk factors: cholesterol > 6.2 mmol/L and/or systolic blood pressure > or = 160 mm Hg and/or diastolic blood pressure > or = 95 mm Hg, and/or because they smoked. Carotid and femoral arteries and the abdominal aorta were assessed by using ultrasonographic methods for the presence of plaque, and subjects were categorized according to the presence (or absence) and extent (one versus two or three sites) of plaque. Plasma fibrinogen was measured according to the thrombin-time method of Clauss. While the presence of atherosclerosis was significantly related to age, current smoking, systolic pressure, LDL cholesterol, and fibrinogen levels, the extent of atherosclerosis was related to age and triglyceride and fibrinogen levels. Multiple regression analysis indicated independent associations between fibrinogen and the presence and extent of atherosclerosis. Plaque prevalence was significantly more pronounced with increasing tertile of fibrinogen levels. The odds ratio of the upper to lower fibrinogen tertiles for the presence of plaque was 1.6 (95% confidence interval, 1.4 to 1.8) and 1.4 (95% confidence interval, 1.2 to 1.7) for its extent. Adjustment for other risk factors slightly reduced the association between fibrinogen and atherosclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)