1. The effects of intradermally injected prostaglandins (PGs) E(1), E(2), F(1alpha) and F(2alpha) have been examined in the rat and in man.2. PGE(1) and PGE(2) 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 PGF(1alpha) and PGF(2alpha) were only slightly active even at a dose of 1 mug.3. Prior administration of mepyramine and methysergide, or depletion of skin mast cell amines with compound 48/80, indicated that PGE(2) exerted its permeability effect in the rat by a release of mast cell amines.4. Nanogramme doses of PGE(1) and PGE(2) or microgramme doses of PGF(1alpha) and PGF(2alpha) injected intradermally into the human forearm induced weal and flare responses.5. It is concluded that prostaglandins E(1) and E(2) can act as intermediates in the production of hyperaemia and oedema resulting from cell damage in the rat and man.