Intrathecal cytokine levels and blood-cerebrospinal fluid (CSF) barrier function were studied in 91 Trypanosoma brucei rhodesiense-infected patients. The CSF concentration of the cellular immune activation marker neopterin and the cytokines IL-6 and IL-10 were increased over control and post-treatment levels in all patients, with maximal levels observed in late-stage (meningoencephalitic) individuals. Analysis of CSF/serum concentration quotients indicated that IL-10 and neopterin were derived from central nervous system synthesis in at least 25% of the patients. Blood-CSF barrier dysfunction occurred in 64% of late-stage patients but not in early-stage patients. While the high level of neopterin observed in the late-stage patient CSF is indicative of widespread cellular activation, the increased levels of IL-6 and IL-10 suggest that counter-inflammatory cellular responses may be important in the regulation of neuropathogenesis in late-stage human African trypanosomiasis.