Increased gut permeability (GP) following burn injury has been implicated in the predisposition to sepsis andmultiple systems organ failure (MSOF). Since previous studies have identified only “global” alterations in GP, we examined the jejunum, ileum colon individually for GP using probes of two different sizes: fluorescein isothiocyanate-dextran-3 (FDEX, molecular weight 4387 d) and horseradish peroxidase (HRP, molecular weight 40,000 d). Animals were examined for GP at 1, 2, or 4 days following burn. The GP was significantly increased in all segments combined following burn injury to both the small probe (FDEX, p < 0.001) and the larger probe (HRP, p < 0.06) versus controls. The GP was significanty greater for FDEX versus HRP (p < 0.001). Jejunal permeability to FDEX and HRP increased most at 24 hours. Ileal and colonic GP to FDEX increased early also, but were higher at days 2 and 4. These results suggest that, following burn injury, there is differential GP that is size and site dependent that increased GP may last well beyond 24 hours postburn despite feeding.