It is well known that different stress paradigms are able to rapidly induce corticosterone production and immune function through the activation of the hypothalamic-pituitary-adrenal axis. It has been reported that glucocorticoids suppress natural killer (NK) activity and interleukin (IL)-1 production and, on the other hand, that IL-1 and IL-6 stimulate the release of corticotrophin-releasing-hormone from the rat hypothalamus. Moreover, it has been reported that IL-12 plays a central role in the initiation of cell-mediated immunity, directly and via its induction of interferon (IFN)-gamma and activation of NK cells. In this study, we examined the effects of water-soluble low-molecular-weight beta-glucan isolated from Aureobasidium pullulans 1A1 strain on the corticosterone levels and immune function, such as NK activity and IL-6 and IL-12 production, using a restraint stress-induced mouse model. The water-soluble low-molecular-weight beta-glucan at a dose of 50 or 100 mg kg(-1) inhibited the increases in the blood corticosterone level and the reduction of NK activity induced by restraint stress. Furthermore, the water-soluble low-molecular-weight beta-glucan (100 mg kg(-1)) prevented the reduction of IL-6 and IL-12 production by splenocytes caused by restraint stress. These findings suggest that the inhibitory actions of water-soluble low-molecular-weight beta-glucan on the increase in corticosterone level and reduction of NK activity induced by restraint stress may be associated with the abrogation of the IL-6 and IL-12 reduction caused by the stress. Thus, water-soluble low-molecularweight beta-glucan may be an effective dietary supplement for the prevention of stress.