The extravasation of Evans blue dye injected in the rat tail vein (EB, 20 mg/kg) was used as a measure of vascular permeability. When the animals were treated with tumor necrosis factor (TNF, 200 micrograms/kg), EB dye was recovered in much larger quantities than in controls in all organs, and especially in the trachea, lower bronchi, lung parenchyma, spleen, pancreas and duodenum (100% increases and over). The EB contents of higher bronchi, heart, liver and kidneys were less marked. The injection of TNF (200 micrograms/kg) 60 min before an injection of platelet-activating factor (PAF, 0.1 micrograms/kg) produced a synergism in many organs. The increases varied from 176 to 574% for the trachea, bronchi, lung parenchyma, pancreas, kidneys and duodenum. The increases in EB contents of the heart, spleen and liver were 86, 96 and 38% respectively. Human recombinant interleukin (IL-1 alpha, up to 400,000 U/kg) did not modify vascular permeability by itself nor primed the effect of PAF in our model. The combination of TNF and IL-1 alpha did not produce effects larger than those of TNF alone. These results further confirm the proinflammatory effects of PAF and its complex interactions with cytokines.