Background: Data addressing the incidence and epidemiology of influenza and influenza-like illness (ILI) in tropical regions of the world is scarce, particularly for the neotropics of South America. Methods: We conducted active, population-based surveillance for ILI across 45 city blocks within the Amazon Basin city of Iquitos, Peru. Demographic data and household characteristics were collected for all participants, and participating households were visited three times weekly to inquire about ILI (fever plus cough or sore throat) among household residents. Nasal and oropharyngeal swabs were collected from participants with ILI and tested for influenza virus infection. Results: Between May 1, 2008 and July 8, 2009, we monitored 10,341 participants for ILI for a total of 11 569·5 person-years. We detected 459 ILI episodes, with 252 (54·9%) of the participants providing specimens. Age-adjusted incidence of ILI was estimated to be 46·7 episodes/1000 person-years. Influenza A and B viruses were detected in 25 (9·9%) and 62 (24·6%) specimens of ILI patients, respectively, for an estimated age-adjusted incidence rate of 16·5 symptomatic influenza virus infections/1000 person-years. Risk factors for ILI included age, household crowding, and use of wood as cooking fuel. For influenza virus infection specifically, age and use of wood as a cooking fuel were also identified as risk factors, but no effect of household crowding was observed. Conclusions: Our results represent the initial population-based description of the epidemiology of ILI in the Amazon region of Peru, which will be useful for developing region-specific strategies for reducing the burden of respiratory disease. © 2010 Blackwell Publishing Ltd.