This chapter discusses the relationship between stressful life events and disease. A number of studies have reported direct measures of immune functioning stressful life experiences. The immune system has two primary tasks, recognition of foreign materials and inactivation and removal of these materials. In animals, a variety of simple physical stressors have shown to alter the development of disease. These functions are accomplished by different, but not independent, cell populations. The chapter examines whether the controllability of a stressor is important in modulating the activity of the immune system. Phagocytic cells, which are involved in the removal of microorganisms, other cells, and foreign materials, include the macrophages and neutrophils. Corticosteroids are released by stressors such as inescapable shock and are known to alter different aspects of immune functioning. A number of lines of evidence suggest that an endogenous opiate may be involved in mediating some of the immunosuppressive effects of stress.