The prevalence of reactive serological tests for syphilis (STS) was investigated in 183 Jamaican patients with tropical spastic paraparesis (TSP) and 200 age and sex matched controls. A significantly higher prevalence of reactive STS was found in TSP patients (34.9%) compared with controls (14.0%, P < 0.001). The biological false positive (BFP) rate was also significantly higher in TSP patients (P < 0.01) as well as controls (P < 0.001) over 40 years of age. However, these findings do not imply a pathogenetic role for treponemal disease in TSP. The high prevalence of reactive STS in Jamaican TSP patients may be multifactorial, and include biological false positives (BFP), previous childhood yaws and concurrent syphilis.