The effect of acute stress on the immune system was examined in mice. Restraint stress decreased the number of lymphocytes in the liver, whereas the number of lymphocytes remained unchanged in the spleen and thymus. In the liver, the decrease in number appeared at 1.5 h and fell to a third of the control level at 3 h. + cells remained constant in the liver under the stress, while those of total T cells and NK cells decreased. The levels of hyaluronan (HA) in various tissues and sera were then examined. The expression of hyaluronan binding protein (HABP) was found to increase in the skin, liver and kidney as shown by immunohistochemical staining. An increase of HA in sera due to stress was seen at 3 h. The present results suggest that the activation of CD44 + T cells and unconventional T cells (i.e., innate immunity) in the blood and the elevated levels of HA (ligand for CD44) in the tissues and blood are crucial responses to acute stress exposure.There have been many reports on the relationship between various stresses and immunological conditions in humans, rats, and mice (4,6,28,30,32,38). Not only physical stress (21,22,28,30,32) but also psychological and psychosocial stress (3,4,8,14,19,38) increases the concentrations of catecholamines (i.e., adrenalin, noradrenalin, and dopamine) in the peripheral blood, resulting in a change in the number of lymphocytes (4,6,8,12,19,20,22,23). As for the clinical importance of stress, acute stress activates inflammation and improves wound healing, vaccination effectiveness and resistance to infection (7,9,10,38), while chronic stress is immunosuppressive (25) and impairs wound healing (11, 29).In the earlier studies, we have investigated the effect of long-term physical stress for 24 h on immunological conditions and found that the stress increased the concentration of catecholamines and corticosterone in the peripheral blood and that the stress changed the proportions of lymphocyte subsets in various tissues (28,30,32). Especially in liver, the percentages of IL-2Rβint cells and NKT cells increased and the cytotoxicities of NK cells and NKT cells were changed by the stress. In the present study, we administered psychological stress to mice, the stress period of 6 h being shorter than that of the previous experiments (24 h) (28,30,32). We investigated herein whether the subsets of IL-2Rβint cells, NKT cells, CD3 + CD44 + cells (i.e., CD44 + T cells) and B cells were influenced by stress. These subsets of lymphocytes are abundant in the liver and are known to be stressresistant (28, 30). The results indicated that the stress clearly changed the number of lymphocytes and the percentages of some lymphocyte subsets in