Fourteen cerebrospinal fluid (CSF) samples obtained from Rhodesian sleeping sickness patients from the Lambwe Valley at relapse were positive for the presence of anti-trypanosomal antibody by both IFAT and ELISA. The mean optical density (o.d.) in the ELISA test was 0.804 +/- 0.362 and ranged from 0.258 to 1.363. CSF from five patients from the same area without evidence of meningoencephalitis were all negative by ELISA (mean o.d. 0.023 +/- 0.016, range 0.011-0.051). Control CSF samples from U.K. patients without Rhodesian sleeping sickness but with elevated levels of CSF total protein were also negative. Antibody detected by ELISA declined after Mel-B treatment of relapse and most samples had returned to negative within two years of treatment. We present evidence that serological evaluation of the CSF by ELISA and/or IFAT can provide supportive evidence of the trypanosomal origin of the infection. This is especially important at the time of relapse, when parasitological diagnosis may be impossible and records of treatment for the primary infection may not be available.