1. The responses of human cutaneous blood vessels to intradermal injection of bradykinin, histamine and 5-hydroxytryptamine (serotonin) are studied in order to evaluate the ability of these agents to mediate the vascular changes of sustained acute inflammation in the skin.2. Bradykinin produces erythema, owing to a direct effect on blood vessels, and wealing. Dose-response studies indicate that bradykinin is more potent than serotonin or histamine in respect of wealing.3. The response to serotonin differs qualitatively as well as quantitatively according to dose. High doses cause wealing and erythema with the characteristics of an axon reflex flare, but low doses produce erythema by a local effect without wealing.4. Using the technique of arterial occlusion, the occurrence of tachyphylaxis in respect of wealing was demonstrated with histamine and serotonin, but not with bradykinin. This evidence suggests that of the three agents, only bradykinin can mediate increased vascular permeability in sustained acute inflammation.5. The specificity of tachyphylaxis and the failure of anti-histamine to antagonize bradykinin wealing suggest that bradykinin and histamine act on separate blood vessel receptors.6. Corticosteroids do not inhibit wealing due to a wide range of doses of bradykinin. The anti-inflammatory activity of corticosteroids may therefore be due to reduced formation of kinins.