Stress results in activation of the hypothalamic pituitary adrenal axis and affects illnesses 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 interleukin-1 (IL-1) and corticotropin-releasing factor (CRF) in this effect. After a restraint stress session colonic segments were isolated and submitted to three 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 with intracerebroventricular (I.C.V.) IL-1ra or alpha-helical CRF9-41, (3) in naive rats pretreated with I.C.V. rhIL-1beta or CRF and (4) in rats treated with central IL-1beta and CRF plus alpha-helical CRF and IL-1ra, respectively (cross-antagonism reaction). Acute stress increases histamine content in colonic mast cells, without degranulation. I.C.V. pretreatment with IL-1ra or alpha-helical CRF9-41 blocked stress-induced mast cell histamine content increase. Both I.C.V. rhIL-1beta and CRF injections reproduced the stress-linked changes. I.C.V. treatment with CRF antagonist blocked I.C.V. rhIL-1beta-induced mast cell histamine content increase, whereas central IL-1ra did not affect stress events induced by I.C.V. CRF administration. These results suggest that in rats acute stress increases colonic mast cell histamine content. This effect is mediated by the release in cascade in the brain first of IL-1 and secondly of CRF.