The murine model of influenza viral infection was used to evaluate the effects of restraint stress on pathogenesis and survival in inbred strains of mice. We recently reported that restraint stress was associated with an enhanced probability of survival in one strain of inbred mouse, DBA/2, and not in another, C57BL/6. Those studies suggested that the protective mechanism(s) of stress on mortality in the DBA/2 mice might be attributable to elevated levels of circulating glucocorticoids. Therefore, daily levels of plasma glucocorticoids were measured during influenza viral infection in both these strains. The present studies demonstrated that influenza infection itself is perceived as a stressor in both C57BL/6 and DBA/2 mice as evidenced by elevated plasma glucocorticoid levels within 48 h of infection. However, augmentation of glucocorticoid levels was not seen in the DBA/2 mice that were also subjected to restraint stress during the course of infection. Thus, corticosterone levels alone did not account for the enhanced survival seen in this group of animals.