T he possible occurrence of immune complexes (IC) in serum and in cerebrospinal fluid (CSF) has been studied in 36 patients with African trypanosomiasis (Trypanosoma brucei gambiense). In serum, very high levels of IC were detectable by the ¹²⁵I-C1q-binding and by the conglutinin-binding assays with positive results in 94 and 87%, respectively, of untreated patients. Circulating IC were found in both early and late stages of the disease, without significant quantitative differences; their size was 15-25S. There was a significant negative correlation between C3 values and C1qBA. Our studies suggest that circulating IC occurring during trypanosomiasis may be the expression of a polyclonal B cell activation. Indeed, there was a significant correlation (P < 0.001) between the levels of circulating IC and either the levels of IgM (mean value 12.5±7.2 mg/ml) or with the levels of rheumatoid factor-like antiimmunoglobulin antibodies that were detected by solid phase radioimmunoassay in 74% of the patients.IC were detected in 31 of 35 CSF samples, with a marked elevation in patients with definite involvement of the central nervous system as compared with earlier stages of sleeping sickness. The occurrence of IC in CSF was not related to an impairment of the blood-brain barrier as shown by analysis of CSF/serum albumin ratios. The level of IC in CSF did not correlate with the serum level and, therefore, circulating IC do not appear to cross efficiently an unimpaired blood-brain barrier. The analysis of IgG, IgM, and albumin concentrations in serum and CSF demonstrates a marked intracerebral immunoglobulin synthesis in patients with manifestations of meningoencephalitis. There was a correlation between CSF-C1q binding assay and this local IgG synthesis.These data are consistent with a local formation of IC in CSF in patients with active meningoencephalitis. The results obtained in eight patients followed during therapy suggest that the presence of IC in CSF may be an indicator of a continuing central nervous system disease and that the quantitation of CSF-IC may be useful for monitoring patient care.