Carrageenan iota and dextran sulfate deplete the plasmatic stores of kininogens in the Rat. 2. A slow intravenous infusion of carrageenan iota in the anaesthetized Rat produces a lowering of blood pressure which is only transient because of the development of tachyphylaxy. At this stage the cardio-vascular system which fails to respond to carrageenan iota injection is also refractory to ellagic acid administration. After depletion of the plasmatic stores of kininogens by dextran sulfate, glandular kallikreins or ellagic acid, carrageenan iota has lost its hypotensive properties. It is concluded that the cardio-vascular effects of carrageenan iota are mainly due to activation of the kininogenskinins system. 3. Indomethacin curtails the hypotensive effects of kinins by inhibition of the release of prostaglandins by these polypeptides. It also reduces the duration of the hypotensive response to carrageenan. Carrageenan iota is neither a histamine nor a 5-hydroxytryptamine liberator.