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Serum cytokine profiles in patients with Plasmodium vivax malaria who presented with and without hyperpyrexia were compared by a retrospective review of the medical records of the consecutive patients seen at the military hospitals near the demilitarized zone in the Republic of Korea from April 2000 through October 2001. Of 162 male patients studied, 120 (86.4%) presented with hyperpyrexia (i.e., an axillary temperature ≥ 40°C). The mean ± SEM ages of the patients with and without hyperpyrexia were 21.5 ± 0.14 and 21.9 ± 0.39 years, respectively (P = 0.33). The mean ± SEM concentrations of serum interleukin (IL)-6 (379.7 ± 44.1 pg/mL versus 105.4 ± 26.8 pg/mL; P = 0.002), IL-10 (583.4 ± 58.2 pg/mL versus 142.4 ± 39.7 pg/mL; P = 0.0001), and interferon-𝛄 (312.6 ± 33.9 pg/mL versus 112.9 ± 27.1 pg/mL; P = 0.0001) were significantly higher in patients with hyperpyrexia compared with those without hyperpyrexia. The mean ± SEM concentrations of serum tumor necrosis factor-α were 155.5 ± 54.5 pg/mL and 109.9 ± 29.3 pg/mL (P = 0.27) in patients who presented with and without hyperpyrexia, respectively. Further studies are needed to examine whether serum concentrations of these cytokines also parallel their concentrations at the tissue sites of their production and action.