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This study was undertaken to investigate the effect of emotional stress on humoral immunoactivity and to examine whether the sympathetic nervous system was involved in the immunomodulation. In the present study, two types of emotional stressors were used. One was footshock apparatus used to cause the rats which were given footshock before, emotional stressed; the other was an empty water bottle used to cause the rats which were trained to drink water at two set times each day, emotional stressed. The effect of emotional stress on the primary immune function (anti-ovallum antibody level and spleen index), the endocrine response (corticosterone level, epinephrine and norepinephrine level), the behavioral changes (freezing, defecation, grooming and attacking behavior) were investigated. The main results were: 1. Two types of emotional stress significantly increased the level of plasma corticosterone, norepinephrine and epinephrine, as well as freezing, defecation and attacking behavior. 2. Two types of emotional stress significantly decreased the level of anti-ovallum antibody. A negative correlation between catecholamine level (epinephrine and norepinephrine) and antibody level or spleen index was found. 3. β-adrenergic receptor antagonist propranolol could reverse the immunomodulation induced by emotional stress. 4. After two types of emotional stress, c-fos expression was observed in the following brain areas or nucleus; arcuate nucleus, anterior commissure nucleus, diffuse part of dorsalmedial nucleus hypothalamus, lateral dorsal nucleus thalamus, medial nucleus amygdala, solitary nucleus, frontal cortex and cingulum. These brain areas and nucleus are involved in the central modulation of the autonomic nervous system. Taken together, these findings demonstrate that emotional stress can suppress humoral immunity and the activation of the sympathetic nervous system is involved in the humoral immunomodulation induced by emotional stress.