Little data are available on how HIV and other sexually transmitted infections (STIs) affect indigenous people in Latin America, including Peru. We conducted a sero-epidemiologic survey of HIV infection and syphilis in a native community, the Chayahuita, an indigenous population in the Amazon region of Peru. The seroprevalences of HIV and syphilis in adults were 7.5% (6 of 80) and 6.3% (5 of 80), respectively. None of the participants had ever used a condom. Male to male sexual behavior was common. At the current levels of HIV prevalence, there is the risk of a negative impact on the survival of the Chayahuita ethnic group as a whole. The outcomes of this study highlight the need for urgent medical and anthropologic approaches to stop HIV transmission in indigenous Amazonian communities. Copyright © 2007 by The American Society of Tropical Medicine and Hygiene.