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Background: Salvador is the city with the highest number of HTLV-1 infected individuals in Brazil, yet the main route of HTLV-1 transmission is unknown. Objective: To investigate the association of syphilis infection as a proxy for sexual transmission of HTLV-1 infection in the general population of this city. Methods: A cross sectional population-based study was conducted with 3,451 serum samples obtained by a representative simple random sampling. Data on gender, age, income, and years of education were collected by questionnaire and the presence of HTLV, HIV and Treponema pallidum infection was determined by serology. Logistic regression analysis was used to evaluate the independent effect of the potential explanatory variables to HTLV-1 infection and Odds Ratios (OR) and 95% CI were calculated. Results: The majority of studied individuals were female (56.4%), had less than 7 years of education (55.3%) and earned two or less minimum wages (52.0%). The overall prevalence of HTLV-1 was 1.48% (51/3,451; 95% CI: 1.10%– 1.94%), which increased with age. Only three persons younger than 17 (3/958; 0.31%; CI 95% 0.06–0.91) years were infected by HTLV-1. Among the 45 syphilis positives, 12 (26.7%) were HTLV positive, while among 21 HIV positives, only one (4.8%) was HTLV positive. HTLV-1 infection was found to be associated with syphilis infection (ORADJUSTED 36.77; 95% CI 14.96–90.41). Conclusion: The data presented herein indicate that horizontal transmission between adults is the main route of HTLV-1 infection in the general population of Salvador and that this is likely to occur through sexual contact. [ABSTRACT FROM AUTHOR]