This is a request for a second renewal of a program project that has involved most of the principles for over eight years. Because of the reorientation of the NIAlD program under which this program project has been funded for the last decade a clinically oriented Demonstration Project has been added and because the focus has increasingly become inflammation (as opposed to the pure genetics of the major histocompatibility complex in man) an additional project has been added. Critical cells of the immune system are being studied in four distinct projects (T cells, macrophages, mast cells and B cells). The role of the major histocompatibility complex, T cell receptors, and antigen presentation are central elements of the immune system and of inflammation. The effector cells of this system, the macrophages and mast cells are also being studied. All of us have shared reagents, technologies, ideas and resources for some years and the addition of a Demonstration Project that is related to a chronic inflammatory disease is a reasonable and natural outgrowth of this longstanding interaction. Core facilities which serve to facilitate interaction as well as promote the sharing of resources are essential. As such, the broad goals of our program should be realizable.