The role of proinflammatory cytokines in the response to acute stressor exposure has received recent attention. Exposure to a single session of inescapable shock (IS) induces peripheral and central proinflammatory cytokines. Other stressors also increase expression of proinflammatory cytokine mRNA and/or protein in various tissues. However, the induction of central and peripheral proinflammatory cytokines by stressors remains controversial and the pattern of cytokine induction is not consistent across stressors. The present experiments sought to examine the pattern of the proinflammatory cytokine response to a stressor known to cause elevations of IL-1β protein. mRNA expression for three proinflammatory cytokines, IL-1β, TNF-α and IL-6, and IL-1β protein was examined after IS. IS increases IL-1β mRNA and/or protein in a variety of tissues, including hypothalamus, hippocampus, pituitary and spleen. Furthermore, IS concomitantly alters IL-1β mRNA and protein in hypothalamus and spleen, while the IL-1β mRNA increase in pituitary lags behind the increase of IL-1β protein. Interestingly, IL-1β mRNA is elevated in hippocampus 4 h after IS, but an increase of IL-1β protein in hippocampus is not detected. Expression of TNF-α and IL-6 mRNA do not increase in response to IS. Indeed, TNF-α mRNA expression decreases in cortex, pituitary and liver immediately after IS. These findings suggest that alterations of proinflammatory cytokine expression by stressors, and IS in particular, are region- and cytokine-specific.