Damage to the gut appears to have a motor role in the development of multiple organ failure (MOF) in cases of severe injury such as septic shock or ionising radiation exposure. Current theories suggest that intestinal damage is associated with the initiation and maintenance of systemic inflammatory-anti-inflammatory responses. One anti-inflammatory therapeutic approach for MOF remains the use of corticosteroids. However the real benefits of these agents are under continual reappraisal. The objective of the present study was to investigate intestinal and vascular function and inflammatory reactions following abdominal irradiation in mice treated or not with the synthetic corticosteroid, Dexamethasone (Dex). Mice (male C57BL/6J) were anaesthetised (xylazine 20 mg kg-1: ketamine 50 mg kg-1 i.p.) and exposed to a total abdominal irradiation (15 Gy, X, 2 Gy/min). Dex treatment (3 mg kg-1 i.p.) was started 2h post exposure and continued for 3 days (functional studies) or 14 days for survival studies with decreased dose from day 7. Animals received antibiotic treatment from day 1 (Baytril, 60 mg kg-1, p.o.). At 4 days animals were anesthetised for in vivo measurement of intestinal (jejunal closed loop) or vascular (intra-vital microscopy) FITC-dextran permeability. Tissues were removed from another group after animals were humanely killed by exsanguination for histological and biochemical analyses. At this dose of irradiation animals lost around 25-30% body weight concomitant with a reduction of food and water intake and a 7-day survival rate of 50%. At 4 days post exposure intestinal structure was severely modified (crypt loss, oedema, inflammatory cell infiltrate) in parallel with increased intestinal cytokine levels TNFalpha, IL-6, KC (p<0.05, N=6). Intestinal permeability increased 3 fold and intestinal enzyme activities (sucrase, Na,K-ATPase) were markedly reduced (-50%). Vascular permeability index (p.i) was increased from 41.2 +/-4.5 (controls N=4) to 83.2 +/-9.7 (irradiated N=4). Dex treatment increased survival (100%) and improved intestinal structure, enzyme activity (sucrase 0 Gy 0.34+/-0.14, 15Gy 0.18+/-0.01, 15 Gy + Dex 0.31+/-0.03 N=14) and vascular permeability (p.i. 44.6+/-9.5 N=4). However gut permeability remained higher in Dex-treated animals. Tissue KC levels were reduced by Dex treatment (-30%). In conclusion, this study provides evidence of a gut inflammatory response concomitant with modifications of gut function post abdominal irradiation and dexamethasone treatment improved survival and intestinal function. All procedures accord with current national and local guidelines.