The mechanism by which chronic stress affects the course of inflammatory diseases is still not well understood. We have evaluated the effect of two types of nonhabituating stress on a major component of the inflammatory response, synovial plasma extravasation, induced by perfusion of the potent inflammatory mediator, bradykinin and evaluated the underlying neuroendocrine mechanism in the rat. Chronic intermittent noise or ether stress induced profound inhibition of bradykinin-induced plasma extravasation, which is associated with increased adjuvant-arthritis severity. This inhibition, however, took 24 h to fully develop after the last exposure to stress and persisted for at least 48 h. The inhibition could be reversed by an additional exposure to the stressor, just prior to measuring the inflammatory response, suggesting that the delay is due to stress-induced release of a factor that acutely masks the inhibition of the inflammatory response. This novel, unexpected feature of the effect of nonhabituating stress on inflammation may help explain variability in effects of stress in patients with inflammatory disease. The effect of nonhabituating stress on inflammation was dependent on the sympathoadrenal axis with no detectable contribution by the hypothalamic–pituitary–adrenal axis.