Objective To evaluate the influence of amphetamine-type stimulants on serum rapid plasma reagent (RPR) tiler and negative conversion rate of RPR in patients with syphilis. Methods Thirty-six patients with syphilis who took amphetamine-type stimulants (ATS) were recruited in this study together with 44 patients with syphilis who never took ATS and 30 normal human controls. Benzathine benzylpenicillin was given intramuscularly to all patients at a dose of 2 400 000 unit per week for 3 weeks. RPR and treponema pallidum particle agglutination (TPPA) assay were performed before treatment, 3, 6, 9 and 12 months after the therapy. Radioimmune assay and ncphelometry were used to detect the serum level of IgG, lgM and IgA. The capability of peripheral blood mononuclear cells (PBMCs) to product interferon-T (IFN-γ) and interleukin-4 (IL-4) was evaluated with ELISA. Results Before treatment, RPR titcr was significantly lower in the stimulant-taking group than in the non-taking group (χ2 = 14.93, P < 0.05). The negative conversion rates were 5.56%, 16.67% and 52.78% in stimulant-taking group 6, 9 and 12 months after the treatment, respectively, significantly lower than those in the control group (all P < 0.05). As for the serum level of IgG, IgM and IgA, there was no significant difference among the stimulant-taking group, non-taking group and normal control group (all P > 0.05). The capability of PBMCs to product IFN-γ was highest in the stimulant-taking group, followed by the non-taking group and normal control group (all P < 0.05). No significant difference was observed in the capability of PBMCs to produce IL-4 between the stimulant-taking group and non-taking group, but a significant increment was noted in these patients compared with the normal human controls (all P < 0.01). Conclusion Amphetamine-type stimulants could reduce serum RPR titer and negative conversion rate of RPR in patients with syphilis, likely by impairing cellular immunity of patients.