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We measured the levels of interferon alpha (IFNα) in the sera of Thai children hospitalized with dengue hemorrhagic fever (DHF) or dengue fever (DF) to examine the role of IFNα in dengue virus infections of humans. The percentage of patients who had detectable levels of IFNα (≥ 3 U/ml) was higher in patients with DHF (80%, P < 0.001) and in patients with DF (60%, P < 0.001) than in healthy Thai children (7%). The levels of IFNα were higher in patients with DHF and in patients with DF on the first few days after the onset of fever than in healthy Thai children. The average levels of IFNα in patients with DHF were high two days before defervescence, decreasing gradually until the day of defervescence. There was a subset of patients with DHF who had increasing levels of IFNα after defervescence. However, the levels of IFNα in patients with DF were not high after fever subsided. The levels of IFNα were not different among children with DHF grades 1, 2 and 3. Among patients with DHF, T lymphocytes were activated to a higher degree in high IFNα producers than in low IFNα producers. These results indicate that similarly high levels of IFNα are produced in vivo during the acute stages of DHF and DF, and that high levels of IFNα remain after fever subsides in some patients with DHF, but not in patients with DF.