The levels of tumor necrosis factor-α (TNF-α) in sera from Trypanosoma brucei gambiense-infected patients from the endemic region of Boko Songho (Bouenza focus in Congo) were measured. An increase was observed in sera from patients (geometric mean = 53.75 pg/ml, n = 69) compared with control subjects from the same endemic area (6.72 pg/ml, n = 31). The patients were classified as being in the early (blood lymphatic) stage and late (meningo-encephalitic) stage of disease according to the presence of parasites and cells in cerebrospinal fluid (CSF). An increase in TNF-α was noted in late stage patients (68.42 pg/ml, n = 28) compared with early stage patients (43.68 pg/ml, n = 41). Those patients with fever, asthenia, and edema and those with neurologic signs had higher levels of TNF-α (89.36 pg/ml, n = 26) than others (38.07 pg/ml, n = 43). No differences in TNF-α levels were seen when trypanosomes were detected in one location (blood, lymph nodes, or CSF) or two or three locations. These data show that the levels of TNF-α in serum of T. b. gambiense-infected patients were correlated with disease severity (presence of signs of inflammation or presence of major neurologic signs) and indicate that TNF-α could be involved in some aspects of human African trypanosomiasis physiopathology.