Stress results in activation of PHA axis and affect illness such as neuroinflammatory syndrome. In vivo acute stress (restraint stress) induces gastrointestinal function disturbances through colonic mast cell activation. This study investigated the effect of acute stress in histamine content of colonic mast cells, and the central role of IL-1 and CRF in this effect. After restraint stress session colonic segments were isolated and submitted to 3 protocols: i) determination of histamine levels by radioimmunoassay (RIA) after incubation with 48/80 compound, ii) evaluation by histology of mucosal mast cell (MMC) number and iii) determination of histamine immunoreactivity of MMC. These procedures were conducted 1) in sham or stressed rats 2) in stressed rats previously treated by icv IL- 1ra or a-helical CRF9-41, 3) in naive rats pretreated by icv rhIL-1 or CRF and 4) in rats treated with central IL-1 and CRF plus a-helical CRF and IL- 1ra respectively (cross antagonism reaction). Acute stress increases histamine content in colonic mast cells, without degranulation. Icv pretreatment with IL- 1ra or a-helical CRF9-41 blocked stress-induced mast cell histamine content increase. Both icv rhIL-1 and CRF injections reproduced the stress-linked changes. Icv treatment with CRF antagonist blocked icv rhIL-1- induced mast cell histamine content increase; whereas, central IL-1ra did not affect stress events induced by icv CRF administration. These results suggest in rats that acute stress increases colonic mast cells histamine content. This effect is mediated by the release in cascade in the brain first of IL-1 and secondly of CRF.