There is considerable evidence that aging is associated with immune system changes. Aging is also characterized by a decreased ability of individuals to adapt to stress which is linked to hypothalamic-pituitary- adrenal axis dysregulation. Evidence supporting a relationship between stress and aging is mounting as studies have shown increased rates of dexamethasone resistance and basal hypersecretion of glucocorticoids in normal elderly humans. Stressors are believed to influence susceptibility to physical disease by causing negative emotional states which negatively affect physiological systems. There is general agreement that there is a link between high levels of social support and good health, although research has not focused as much on the elderly as on the overall population. Recent data has shown that post-menopausal women.show a significantly lower number of total lymphocytes than fertile women. Hormone replacement therapy (HRT) is becoming more frequent and although its effect on osteoporosis, cancer, and heart disease has been studied, little work to date has focused on its effect on the immune system. Although clinical studies are highly relevant, such work sometimes does not permit the specificity of variables or degree of control which may be obtained using animal models. By comparing older and prime aged female rhesus monkeys and using social manipulations that are based on routine management procedures, the proposed series of studies will test specific hypotheses regarding: 1) the ability of old females to adapt to stress, 2) the effect of stress on the pituitary-adrenocortical axis and the immune system (using functional measures), 3) the effect of social companionship and reactivity in modulating stress and 4) the effect of HRT on immune system measures in ovariectomized females. The resultant data may help elucidate the stress-related immune and endocrine changes occurring with age and the role of social support and an individual's reactivity in modulating stress.