Summary1. The time course of oedema formation in rats caused by injection of carrageenin into the paw was followed for 5-5 hours. Intact or adrenalectomized rats which had previously been injected with ellagic acid or saliva to reduce considerably the concentration of blood kininogens, or with methysergide to antagonize 5-hydroxytryptamine (5-HT) showed a reduced inflammatory response. It was concluded that kinins and 5-HT contributed significantly to oedema formation during this period. 2. Mepyramine alone had no effect on oedema formation, but in combination with ellagic acid treatment, with or without methysergide, it caused a reduction suggesting that histamine played a minor role in oedema formation during the first 3 hours. 3. Vascular permeability studies indicated that injection of ellagic acid did not interfere with the normal responses in skin to intradermal injections of histamine, 5-HT, bradykinin or compound 48/80. Mepyramine and methysergide, at the doses used in the carrageenin experiments, completely antagonized histamine and 5-HT, respectively, and did not affect the skin responses of bradykinin. 4. Treatment in vivo with ellagic acid or rat saliva was equally effective in reducing plasma kininogen concentrations by an amount equivalent to more than 10 times the quantity of substrate 1 measured by Gautvik & Rugstad (1967). 5. Rat saliva, but not ellagic acid, lowered complement levels by approximately 20%.

Summary1. The effects of intradermally injected prostaglandins (PGs) E1, E2, Fia and F2a have been examined in the rat and in man.2. PGE, and PGE2 caused an increase in local vascular permeability in rat skin; their potency was comparable with that of other putative mediators of inflammation (histamine, bradykinin, and 5-hydroxytryptamine), but PGFia and PGF2a were only slightly active even at a dose of 1 jug. 3. Prior administration of mepyramine and methysergide, or depletion of skin mast cell amines with compound 48/80, indicated that PGE2 exerted its permeability effect in the rat by a release of mast cell amines.4. Nanogramme doses of PGE1 and PGE2 or microgramme doses of PGFia and PGF2a injected intradermally into the human forearm induced weal and flare responses. 5. It is concluded that prostaglandins E1 and E2 can act as intermediates in the production of hyperaemia and oedema resulting from cell damage in the rat and man.

Summary1. Increases in permeability observed after intradermal injection of prostaglandins PGE1 or PGE2 (0 1 Mtg) into rats were greatly reduced when they were given in admixture with PGF2a. This effect was not seen with PGFia at doses of 0 5-1 Mug. 2. Effects of the histamine releasing agent compound 48/80 (25 ng) were inhibited by PGF2a (0-5 MLg) but not by PGFia (0 5 Mug).3. Responses to histamine (1 pg), 5-hydroxytryptamine (0 1 MLg) and bradykinin (1 ug), which have a direct action on the microvasculature, were not significantly altered by PGF2a (0-5 ,ug). 4. It is concluded that PGF2a probably acts by interfering with the release of mast cell histamine by PGE1, PGE2 and compound 48/80. IntroductionProstaglandin E2 (PGE2) has been identified in rat inflammatory exudate (Willis, 1969(Willis, , 1971) and we (Crunkhorn & Willis, 1969, 1971 have recently found that intradermal PGE1 and PGE2 are potent inducers of local vascular permeability in the rat and man. In the rat the effects of PGE1 and PGE2 were apparently mediated via release of histamine and 5-hydroxytryptamine from skin mast cells; PGFia and PGF2a caused little change in local vascular permeability even in doses of up to