Glucocorticoids are potent antiinflammatory agents. They inhibit leukocyte chemotaxis and vascular permeability and generally suppress the expression of many inflammatory mediators. Recent reports suggested that somatostatin (Sms) had significant immunomodulatory properties in vitro and in vivo. In this study we examined the effects of glucocorticoids on immunoreactive somatostatin expression in aseptic inflammatory sites of Sprague-Dawley rats given carrageenin sc. The progress of the inflammatory reaction was studied over a 7-h period with respect to the volume and cellularity of the exudate and the levels of the inflammatory mediators expressed in the inflammatory site, including immunoreactive substance P (sP), corticotropin-releasing hormone (CRH), and tumor necrosis factor-alpha (TNF alpha). Dexamethasone significantly reduced the volume and cellularity of the inflammatory exudates; in parallel, the levels of immunoreactive sP, CRH, and TNF alpha were significantly suppressed by this glucocorticoid. In contrast, immunoreactive Sms was stimulated by dexamethasone in a time-dependent fashion. These findings suggest another mechanism for suppression of the inflammatory reaction by glucocorticoids via stimulation of local Sms expression, which occurs in parallel to the inhibition of the local inflammatory mediators sP, CRH, and TNF alpha.