To study the contribution of inflammatory mediators to the pathogenesis of yellow fever (YF), the serum levels of several cytokines and chemokines were measured in 7 patients with fatal YF (f-YF), 11 patients with nonfatal hemorrhagic YF (nf/h-YF), and 18 patients with nonfatal nonhemorrhagic YF (nf/nh-YF). The levels of interleukin (IL)-6, monocyte chemoattractant protein-1, interferon-inducible protein (IP)-10, tumor necrosis factor- alpha , and IL-1 receptor antagonist (IL-1RA) were all statistically significantly higher in the patients with f-YF than in those with nf/nh-YF. In patients with nf/h-YF, only levels of IP-10 and IL-1RA were significantly elevated. The high levels of pro- and anti-inflammatory cytokines and chemokines in serum from patients with f-YF are reminiscent of those seen in patients with bacterial sepsis. This finding has implications for the understanding of the pathophysiology of YF and the development of therapeutic strategies.