Epidemiological studies of exposed human populations can provide valuable evidence of human health effects. Information has been sparse on human health effects associated with consumption of contaminated Great Lakes fish. As part of its Great Lakes Human Health Effects Research Program, the Agency for Toxic Substances and Disease Registry (ATSDR) has funded ten projects. Of these studies, eight are epidemiologic investigations of human exposure and potential health effects from consumption of contaminated fish. To strengthen and to enhance the findings and comparability across the health studies, ATSDR has initiated several activities. These activities include harmonizing questionnaires, analytical protocols, human health end points, and contaminants tested. Also included is the establishment of a quality assurance and quality control (QA/QC) program and tissue bank. These activities will allow ATSDR to enhance exposure assessment in the Great Lakes basin. In addition, these research activities allow ATSDR to evaluate and to interpret data across all the projects, including a basin-wide health risk analysis on exposure, levels of contaminants or body burden, and the potential for human health effects from exposure to Great Lakes contaminants.