1. The isolated perfused rabbit ear connected to the body by its nerve only was used to investigate the influence of mepacrine on the algesic effect of bradykinin and acetylcholine. For comparison, quinidine was included in this investigation. 2. Infusion of mepacrine or quindine (2-10 microgram/ml) into the rabbit ear reduces the algesic effect of bradykinin as well as of acetylcholine in proportion to the dose. 3. Infusion of postglandin E1 (10 ng/ml) in addition to mepacrine or quinidine restores theinhibited algesic effect of bradykinin more than that of acetylcholine. 4. Mepacrine and quinidine (10 microgram/ml) reduce the brief vasoconstriction elicited by bradykinin in the rabbit ear. 5. The results suggest that mepacrine or quinidine reduce the algesic effect of bradykinin primarily by inhibiting the release of E-type prostaglandins which sensitize pain receptors and secondarily by an unspecific antagonism (local-anaesthetic action). The effect of acetylcholine, however, appears to be reduced mainly by an unspecific antagonism.