Systemic administration of capsaicin elicits heat production, which can be observed in decerebrated preparations but is blocked by spinal transection. To identify the critical locus involved in the capsaicin-induced thermogenesis in the brainstem, we studied the effect of capsaicin on rats with bilateral electrolytic lesions in the premotor areas of sympathoadrenal preganglionic neurons. Lesions in the rostral ventrolateral medulla (RVLM), but not in other regions, largely attenuated the capsaicin-induced heat production. Unilateral microinjection of 30-100 nl capsaicin (0.5%, w/v) into the RVLM elicited a heat production response, whereas capsaicin injection in neighboring areas or vehicle injection into the RVLM did not affect heat production. These results suggest that the thermogenic effect of capsaicin is mediated, at least in part, by some capsaicin-sensitive structure in the RVLM.