The mission of the Environmental Protection Agency (the Agency) is to protect public health and safeguard the natural environment risk assessment. Risk management is an integral part of this mission. The Human Health Research Program (HHRP) Multi-Year Plan (MYP) describes the strategic approach for research to improve human health risk assessment-risk management (RA-RM) processes at the Agency. This MYP, developed by the Agencys Office of Research and Development (ORD), outlines a mission-oriented research effort to provide broadly applicable, more fundamental scientific information and tools that will improve the many problem-driven RA-RM decisions throughout the Agencys Program and Regional Offices. The main objective of the HHRP is to reduce uncertainties in the extrapolations necessary in the risk assessment process by providing a greater understanding of the fundamental determinants of exposure and dose and the basic biological changes that follow exposure to environmental toxicants. The research proposed in this MYP is based on the needs of the Agencys Program and Regional Offices articulated during the spring and summer of 2005, recommendations of the Human Health Subcommittee of the Board of Scientific Directors (BOSC) during their review of the HHRP on February 28-March 2, 2005, and results from a review of the HHRP by the Office of Management and Budget during FY05. Research described in this HHRP MYP is consistent with themes described in ORDs Human Health Research Strategy and the Agencys 2003 Strategic Plan, and builds on work articulated in the 2003 Human Health Research Multi-Year Plan.