Standard burns were sequentially produced on the backs of Sprague-Dawley rats at 0, 1, 2 and 2.5 h, followed by the IV injection of Evans blue dye. All animals were killed at 3 h. Burns were evaluated by wet/dry weight ratios and Evans blue extravasation scored 1-4 by 2 observers. Five groups of rats were compared to controls. Rats made neutropenic by exposure to 137Cs showed no significant difference in wet/dry weight ratio or Evans blue extravasation compared to controls. At 1.5 h 4 other groups were treated with various inhibitors of arachidonic acid metabolism including ibuprofen, a cyclo-oxygenase inhibitor; FPL 55712 [7-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)-2-hydroxypropoxy]-4-oxo-8-propyl-4H-1-benzopyran-2-carboxylic acid], a leukotriene (LT) receptor antagonist; ketoconazole, an inhibitor of thromboxane (Tx) synthetase and lodoxamide, a Ca channel inhibitor. All treated groups showed significant reduction of Evans blue dye extravasation. Wet/dry weight ratios were significantly reduced in rats treated with FPL 55712 and ketoconazole before or after burning. Oxygenation products of arachidonic acid, particularly Tx and LT, are important mediators in early burn edema.