Interleukin 10 (IL-10) is a potent anti-inflammatory cytokine. Increased production of IL-10 has been found in late syphilis, presumably creating favorable conditions for bacteria persistence. Single-nucleotide polymorphisms (SNPs) within the promoter of IL-10 gene have been found to influence IL-10 production. We investigated whether SNPs in the IL-10 gene promoter are associated with cerebrospinal fluid (CSF) levels of IL-10 and neurosyphilis.Polymorphisms in the gene for IL-10 (G→A mutation at the position −1084 and C→A mutation at the position −592) were sought in 35 patients with syphilis and 24 healthy volunteers. CSF examination (i.e. routine laboratory tests and IL-10 levels) was performed in all syphilis patients. Neurosyphilis was defined as reactive CSF VDRL test or CSF white blood cells⩾5/μL and CSF protein concentration⩾45mg/dL.Overall, 31% of patients with syphilis had neurosyphilis. CSF IL-10 levels were significantly higher in patients with neurosyphilis when compared to those with syphilis but not neurosyphilis. −1082 GG and −592 CC genotypes were significantly associated with higher CSF IL-10 levels. Moreover, these genotypes were found to be more frequent in individuals with neurosyphilis in comparison to those without neurosyphilis.Anti-inflammatory immune response seems to be important in pathogenesis of neurosyphilis. Our data suggest that host-related factors, such as SNPs of immune regulatory genes may influence the susceptibility to neurosyphilis.