OBJECTIVE. Our goal was to estimate the impact of a Shigella vaccine in an area where shigellosis is endemic by characterizing the disease burden and antibiotic-resistance profiles of isolates and by determining the prevalence of Shigella flexneri serotypes. PATIENTS AND METHODS. We conducted a 43-month-long prospective, community-based diarrheal disease surveillance in 442 children <72 months of age in the Peruvian Amazon between October 1, 2002, and April 15, 2006. RESULTS. The incidence of diarrheal disease was 4.38 episodes per child-year. The incidence rate for shigellosis was 0.34 episodes per child-year in children <72 months of age and peaked in children between 12 and 23 months at 0.43 episodes per child-year. Maternal education at or beyond the primary grade level, piped water supply, weight-for-age z score, and improved water-storage practices were the most significant determinants of disease in this community with living conditions comparable to many rural areas in the developing world. CONCLUSIONS. Children living in this region had a 20-fold higher rate of disease incidence detected by active surveillance as those recently estimated by passive detection. Most symptomatic disease was caused by S flexneri, although the diversity of serotypes will require a multivalent vaccine to have a significant impact on the burden of disease caused by shigellosis. Several other public health disease-control interventions targeted at water source and improved storage, nutritional interventions, and improved maternal education seem to have a greater impact than a univalent S flexneri 2a vaccine. Copyright © 2008 by the American Academy of Pediatrics.