The acute phase reaction is important in many disease processes. Habitual levels of the acute phase proteins fibrinogen, C-reactive protein (CRP) and interleukin-6 (IL-6) are associated with an increased risk of cardiovascular disease, but the dynamic variation of plasma levels of acute phase proteins may be of importance as well. The aim of this study was to document the variation in response by fibrinogen, CRP and IL-6 levels to a mild inflammatory stimulus (yellow fever vaccination) in 25 healthy individuals. Plasma levels of fibrinogen, CRP and IL-6 were determined at baseline and 7 days after vaccination, and genetic polymorphisms in these genes were determined. After vaccination, fibrinogen levels had changed between −13 and +44% (P = 0.003), CRP levels between −88 and +672% (not significant), and IL-6 levels between −55 and +448% (not significant). Genetic variation partly explained the interindividual variation in response, as IL-6 −174G homozygotes showed a significantly stronger increase in CRP levels than IL-6 −174C allele carriers. In conclusion, this study suggests that a large interindividual variation exists in the acute phase response to yellow fever vaccination, indicating that individuals may be classified as hyper-responders or hypo-responders, and that genetic variation may influence the responsiveness of an individual.