Background: In 2004, cases of HIV and syphilis were reported in an indigenous community in the Peruvian Amazon. This study sought to determine the prevalence of HIV and syphilis in four remote communities of the same indigenous ethnic group located further from an urban center than the original community, and to identify risk factors for HIV and syphilis transmission. Methods: Rapid and confirmatory tests for HIV and syphilis were performed. A questionnaire elicited demographic information, risk factors for sexually transmitted infections, and knowledge/beliefs about HIV/AIDS. Results: We collected 282 blood samples and conducted interviews with 281 (99.6%) participants. The confirmed syphilis prevalence rate was 3.2% (9/282; 3.7% (5/135) for men and 2.7% (4/147) for women). The confirmed HIV prevalence rate was 0.7% (2/282), with both infections in men who had sex with men (MSM). Self-reported MSM activity was 39.7%. There was poor knowledge about HIV infection, transmission, and prevention, and low acceptance of known prevention methods. Conclusions: HIV and syphilis are now prevalent in remote Amazonian communities of an indigenous group in Peru. Expansion of the HIV epidemic into the Amazon requires an urgent public health response. © 2008 International Society for Infectious Diseases.