Diseases of the liver account for substantial morbidity and mortality on a worldwide basis. Many important liver diseases entail an immuno-inflammatory component. In January 1999, we organized a highly successful interdisciplinary conference on Hepatic Inflammation and Immunity that focused on basic immunologic mechanisms in the liver and their roles in health and disease. We propose to build on the success of that meeting in organizing Hepatic Inflammation and Immunity 2002. The ability of many infectious agents to establish persistent infections within the liver may well reflect unique aspects of the intrahepatic immune system, which are also manifest in the muted immune response to liver allografts. For example, hepatitis C virus (HCV) currently infects about 3.8 million Americans and efforts to develop better methods for control of this infection are dependent upon a better understanding of immunologic mechanisms that are active within the liver. This conference is deliberately structured to break down traditional divisions between different groups of researchers whose work involves the immunology of the liver. To achieve this goal, the conference sessions are organized not around areas of hepatology or immunobiology, but around specific hypotheses. These hypotheses have been constructed to address current basic issues in the interaction between antigens, the immune system and the liver. Within each session, researchers involved in diverse areas will present their data and ideas side-by-side. The hypotheses are: 1: The distinctive liver architecture, unusual resident liver lymphocytes and the trafficking pattern of leukocytes through the liver contribute to the unusual pattern of tolerance, immunity and pathology in this organ. 2: The liver induces T cell tolerance by killing T cells. 3: Liver pathogens use multiple complementary strategies to avoid T cell immunity. 4: Death receptors on liver cells are instrumental in both hepatocyte damage and regeneration. 5: Liver lymphocytes control liver regeneration and fibrosis. 6: "NK cells make all the difference," by which we mean to imply that NK cells control the nature of T cell responses in the liver. The meeting will conclude with a discussion in which the hypotheses will be re visited and evaluated. We anticipate that 100-150 scientists from throughout the world will attend this meeting, which should be of value to both clinicians and basic scientists. We hope to bring more outstanding researchers into the field and thus seek R13 support to enable students and postdoctoral fellows to attend.