Plasma and cerebrospinal fluid (CSF) concentrations of nitrate and the cytokines interferon (IFN)–γ, tumor necrosis factor (TNF)–α, interleukin (IL)–10, and IL-4 were measured in 91 African trypanosomiasis patients before and after treatment. Nitrate levels overall were not significantly elevated over those for control persons, but a marginal increase in plasma nitrate was detected in patients reporting illness of <40 days' duration. Plasma IFN-γ and total TNF-α concentrations increased during infection, but free TNF-α levels were low in all patients. The most dramatic cytokine response was for IL-10, which was significantly elevated in both plasma and CSF during infection but returned to control levels after treatment. The results indicate that human African trypanosomiasis leads to the development of a strong anti-inflammatory cytokine response