In the pyramidal cat, an intense and potentially lethal hypotensive response may be evoked by stimulation of a narrow zone dorsal to the median raphe of the posterior medulla. The present investigation concerns some of the pharmacology and hemodynamics of this response. The evidence suggested that an active vasodilator was released into the systemic circulation. The delay observed between the period of medullary stimulation and the cardiovascular response was attributed to either the time involved in the release process or the time required for the substance to reach the general circulation. Pharmacological and chemical isotopic analysis based on the incorporation of histidine-C14 into histamine-C14 indicated that histamine release was associated with the fall in systemic pressure and increase in blood flow. Since atropine blocks the response, as do the antihistaminics, a cholinergic mechanism may be involved in the release process.