Background The renewed interest in community participation in health research is linked to its potential for bridging gaps between research and practice. Its main attributes are the generation of knowledge that can lead to socially robust, long-lasting solutions and the creation of a colearner relationship between researchers and research users. Following this philosophy, Ecohealth has evolved into a specialized framework for participatory research on the impact of pollution on ecosystems and human health. However, its principles pose considerable challenges. Its outcomes are strongly influenced by contextual factors that are impossible to control for ahead of time. This paper describes how the Ecohealth principles were applied to an epidemiological study of heavy metals exposure among indigenous communities of the Peruvian Amazon. It illustrates how knowledge generated from participatory research does not necessarily imply solving a public health problem. This study aimed to contribute to the understanding of the benefits and barriers of following the basic principles of the Ecohealth approach, and assist researchers working in similar contexts. Research process Based upon their personal experience as participant observers, the authors describe the research process; then, they discuss the most important challenges faced, their implications, and the attempted strategies for resolution. Challenges Challenges were grouped into four themes: (1) building trust; (2) one partnership, many stakeholders, multiple agendas; (3) being a researcher; and (4) communicating complex and unexpected findings. Conclusions Integrating the principles of transdisciplinarity and participation posed a series of challenges to the research process that were difficult, and sometimes impossible to overcome. However, positive outcomes from this experience were the lessons learned by the different actors. Despite the lack of immediate action, it is expected that useful interventions to prevent and control lead exposure in the Corrientes population will be implemented in the medium term.