We studied the effects of lesions in the ventrolateral medulla, in a region coinciding with the cell bodies of the A1 group of catecholamine neurons. After bilateral electrolytic lesions at three contiguous rostrocaudal levels (obex and at 1 and 2 mm caudal to the obex), mean arterial pressure increased by 40 mm Hg in the conscious rabbit. This rise in pressure was associated with increased resistance in the distal aortic vascular bed and with profound bradycardia. Many lesioned animals developed respiratory distress in the first few postoperative hours and died with hemorrhagic pulmonary edema. In surviving rabbits, the distal aortic resistance remained raised throughout the 2-week observation period, but the blood pressure and heart rate returned to preoperative levels within 2 hours and then remained normal. Bilateral electrolytic lesions restricted to the level of the obex or to a level 1 mm caudal to the obex also caused transient hypertension and bradycardia, but most of the animals survived this more restricted damage and did not develop pulmonary edema. Micro injections of kainic acid, a neurotoxin that specifically damages cell bodies, also caused transient hypertension and bradycardia, and after larger doses the rabbits died with acute pulmonary edema. Injections of 6-hydroxydopamine caused similar changes in pressure and heart rate, but doses necessary to destroy the A1 cells caused nonspecific histological damage of an extent similar to that produced by electrolytic lesions. Sham-lesioned animals and those with control lesions in adjacent sites did not develop these cardiovascular changes. These experiments suggest that the persistent increase in peripheral resistance after lesions of the ventrolateral medulla results from destruction of neurons that normally act to inhibit sympathetic vasoconstrictor tone. It is our hypothesis that the increase in vascular resistance after the lesions results from destruction of the A1 catecholamine cells within this ventrolateral region.