The present study analyses the effect of IL-1 beta (10 ng i.c.v.) on the hypothalamic serotonergic system and the modulatory role of glucocorticoids. Changes in the serotonin metabolite 5-hydroxyindolacetic acid (5-HIAA) were recorded in freely moving rats by in vivo voltammetry using chronically implanted carbon fiber electrodes (8 microns) in the medial preoptic area. IL-1 beta induced a dual increase in 5HIAA levels: a rapid, short-term rise was followed by a lasting increase possibly due to newly synthesized IL-1. The synthetic glucocorticoid dexamethasone (DEX, 3 mg/kg i.p., 30 min before IL-1 beta), prevented the effect of IL-1 beta starting from 150 min, suggesting that it only inhibited the second increase. In adrenalectomized rats IL-1 beta had no effect but when these rats were given DEX (40 micrograms/kg a day for 3 days) the short-term increase was restored. The glucocorticoid receptor antagonist RU38486 (25 mg/kg s.c., 60 min before IL-1 beta) completely prevented IL-1 beta activation of the serotonergic system. The results indicate that the glucocorticoids are effective inhibitors of IL-1 synthesis but that they play a permissive role on IL-1 beta induced activation of the serotonergic system.