The effects of anaphylaxis on vascular protein extravasation in selected tissues and on the release of prostaglandins in the peritoneal cavity were studied in sensitized rats. Extravasation of Evans blue dye was used as a measure of vascular permeability. Specific antigen challenge increased by 279, 297, 328, 250, and 192% the protein extravasation in the trachea, upper and lower bronchi, pancreas, and duodenum, respectively, but did not modify significantly the vascular permeability of the lung parenchyma, heart, liver, and kidney. Extravasation of Evans blue dye also was increased by 43-fold in the peritoneal cavity. Pretreatment of the animals with indomethacin (10 mg/kg) did not modify significantly the protein extravasation of the trachea, upper and lower bronchi, pancreas, and duodenum induced by anaphylaxis. Pretreatment with a mixture of mepyramine (3 mg/kg) and methysergide (2.5 mg/kg) reduced by 62, 66, and 40% the protein extravasation in the trachea, upper bronchi, and peritoneal cavity, respectively, in similar conditions. The PAF antagonist BN-52021 (5 mg/kg) very strongly reduced the protein extravasation elicited by anaphylaxis in the trachea, upper and lower bronchi, pancreas, and duodenum by 72, 87, 82, 67, and 85%, respectively, and by 53% in the peritoneal cavity. Anaphylaxis also increased the concentrations of thromboxane B2 and leukotriene B4 in the peritoneal exudates, but prostaglandin E2 levels were not affected. Pretreatment with BN-52021 reduced by 29 and 75% the level of thromboxane B2 and leukotriene B4 in the exudates. These results suggest that PAF, histamine, and serotonin mediate the protein extravasation associated with anaphylaxis, whereas prostaglandins are likely to play a minor role in this reaction.