1Concentration-related dye leakage produced by intracutaneous injections of irritants was measured in rats by an Evans blue technique. 2 In rats pretreated with a total dose of 50 mg capsaicin over 4 days, the response to capsaicin, formalin, HC1, KCI, prostaglandin E,, bradykinin and bradykinin with prostaglandin E1 (10-6 M) were greatly reduced, the responses to histamine and 5-hydroxytryptamine were slightly reduced and those to adenosine 5'-triphosphate (ATP) and compound 48/80 were unaffected.3 Pretreatment with intracutaneous injections of compound 48/80 (0.5 ,ug, 24 and 48 h previously) recuded the responses to ATP, compound 48/80, HCI, KCI, prostaglandin E1, and bradykinin but did not affect those to histamine, 5-hydroxytryptamine or bradykinin with prostaglandin E1 (106 M). 4 Responses to capsaicin and formalin produced spotted blueing extending over a large area and were suppressed by compound 48/80 in the smaller pretreated area only. Capsaicin responses were reduced with larger doses of compound 48/80 (total dose 15 gg).