BACKGROUND Systematic-review methodologies provide objectivity and transparency to the process of collecting and synthesizing scientific evidence in reaching conclusions on specific research questions. There is increasing interest in applying these procedures to address environmental health questions. OBJECTIVES The goal was to develop a systematic-review framework to address environmental health questions by extending approaches developed for clinical medicine to handle the breadth of data relevant to environmental health sciences (e.g., human, animal, and mechanistic studies). METHODS The Office of Health Assessment and Translation (OHAT) adapted guidance from authorities on systematic-review and sought advice during development of the OHAT Approach through consultation with technical experts in systematic review and human health assessments, as well as scientific advisory groups and the public. The method was refined by considering expert and public comments and through application to case studies. RESULTS AND DISCUSSION Here we present a seven-step framework for systematic review and evidence integration for reaching hazard identification conclusions: 1) problem formulation and protocol development, 2) search for and select studies for inclusion, 3) extract data from studies, 4) assess the quality or risk of bias of individual studies, 5) rate the confidence in the body of evidence, 6) translate the confidence ratings into levels of evidence, and 7) integrate the information from different evidence streams (human, animal, and "other relevant data" including mechanistic or in vitro studies) to develop hazard identification conclusions. CONCLUSION The principles of systematic review can be successfully applied to environmental health questions to provide greater objectivity and transparency to the process of developing conclusions.