The β-fibrinogen G/A-455 polymorphism genotype along with plasma fibrinogen levels was determined in 482 healthy middle-aged men, of whom 231 were smokers. Smokers had the highest plasma fibrinogen levels (2.92 g/1), ex-smokers the next (2.73 g/1), and never-smokers the lowest levels (2.66 g/1, P < 0.001). Those with one or two A-455 alleles had significantly higher plasma fibrinogen levels in never-smokers and ex-smokers (8.2% and 9.0%, respectively, P < 0.05), and the effect was larger in younger men (45 < 55 years, 11.6%, P = 0.002) than older men (> 65 years, 4.5%, NS), and was not significant in smokers (2.4%, P > 0.05). Allele frequencies were calculated and compared across age groups and between smokers and non-smokers. The difference in frequency of the A-455 allele between smokers and non-smokers varied significantly with age (P < 0.01), with the frequency of the A-455 allele being significantly lower in smokers than in non-smokers in subjects aged > 65 years (P < 0.05), but not in younger men. This demonstrates an interaction between age, smoking and allele frequency of the G/A-455 polymorphism in this population-based sample.