Project Abstract This research proposal, entitled “Familial force of infection and dengue disease burden in Thailand” involves studies in the United States and Thailand to understand how members within a family of all ages respond to exposure to dengue virus and what their clinical outcome is if infected. This is a unique study following 500 families and approximately 3,000 family members in Northern Thailand over a total of 10 years to understand how people’s response to infection changes over time and to different types of dengue virus. This study will allow us to understand the immune response from multiple ages in one family; understand how people are protected from infection or not; and determine the factors on how dengue is spread in the population. This project is a unique opportunity to follow families across 10 years of intense exposure to dengue transmission in an area hyperendemic for dengue. Project activities focus on defining the familial burden of dengue infection, understanding the role of herd immunity in transmission dynamics, and identifying correlates of protection and correlates of disease severity. These activities are derived from our central objectives of understanding dengue pathogenesis and identifying risk factors for infection and transmission. This project and its objectives are highly relevant to the overall objectives of the Program Project which are to advance methods to prevent and treat dengue-related infection and illness.