The relation of daily energy expenditure (EE) and maximal oxygen uptake (VO2max) to plasma fibrinogen with reference to DNA polymorphism was analyzed in a random sample of men (N = 189), age 50-60. Fibrinogen polymorphism was detected using polymerase chain reaction (PCR) and digestion with HindIII and BclI (beta-fibrinogen), and TaqI (alpha-fibrinogen) restriction enzymes. Mean VO2max was 29.4 ml.kg-1.min-1 (95%CI 28.5; 30.2) and mean daily EE was 179 kJ.kg-1.d-1 (173; 186) and were similar in all fibrinogen genotypes. Plasma fibrinogen was 3.26 g.1-1 (3.18; 3.34) and did not associate with fibrinogen polymorphisms. Both EE and VO2max related inversely to fibrinogen level (r = -0.24, P < 0.001). Strongest predictors of plasma fibrinogen were VO2max in TaqI 800 bp homozygotes, and EE together with smoking in TaqI 900 bp homozygotes. The predictive role of VO2max was marginal in the common beta-fibrinogen genotypes, whereas physical activity level explained up to 9% of the variance in the less frequent genotypes. These data suggest that the association of VO2max and EE with plasma fibrinogen varies across the fibrinogen genotypes.