Elevated total cholesterol and plasma fibrinogen levels and smoking are risk factors for cardiovascular disease, whose inter-relationships are influenced by both gender and age. The aim of this study was to investigate the effect of smoking on fibrinogen levels in a hypercholesterolemic population subdivided on the basis of gender and age. The study included 492 hypercholesterolemic subjects, divided into four subpopulations: men and women, aged 26-49 and 50-66 years. Mean fibrinogen levels among smokers and non-smokers in the four subpopulations of this hypercholesterolemic cohort followed mean total cholesterol levels. Three subpopulations (men <50 years, men >/=50 years and women >/=50 years) showed differences in mean total cholesterol and fibrinogen values between smokers and non-smokers (total cholesterol 7.23+/-0.54 vs. 7.40+/-0.93 mmol/l and fibrinogen 2.79+/-0.48 vs. 3.23+/-0.72 g/l in men <50 years; total cholesterol 7.17+/-0.43 vs. 7.50+/-0.60 mmol/l and fibrinogen 3.11+/-0.44 vs. 3.68+/-0.66 g/l in men >/=50 years and 7.41+/-0.59 vs. 7.65+/-0.73 mmol/l and fibrinogen 3.29+/-0.61 vs. 3.58+/-0.71 g/l in women >/=50 years). These values correspond to a percentage difference between smokers and nonsmokers in total cholesterol and fibrinogen of 2.4% and 15.8% in men <50 years, 4.6% and 18.3% in men >/=50 years and 3.2% and 8.8% in women >/=50 years. All differences were significant ( P<0.05), except for total cholesterol in the younger men (<50 years). No differences between smokers and non-smokers were observed in the younger female group (<50 years). Except in the younger female group (<50 years), significant differences between smokers and non-smokers were also observed in the number of subjects exceeding the upper reference value of fibrinogen (>4.0 g/l), the highest percentage being found for the older women smokers (>/=50 years) (29%). In Conclusion, smoking elevates fibrinogen levels in hypercholesterolemic men (<50 years; >/=50 years) and older women (>/=50 years), but not in younger women (<50 years).