The physiological function of L-carnosine (-alanyl-L-histidine) synthesized in mammalian muscles until recently has been unclear. Previously, we observed that intravenous (IV) injection of L-carnosine suppressed renal sympathetic nerve activity (RSNA) in urethane-anesthetized rats, and L-carnosine administered via the diet inhibited the elevation of blood pressure (BP) in DOCA-salt hypertensive rats. To identify the mechanism, we examined effects of IV or intra-lateral cerebral ventricular (LCV) injection of various doses of L-carnosine on RSNA and BP in urethane-anesthetized rats. Lower doses (IV, 1 µg; LCV, 0.01 µg) of L-carnosine significantly suppressed RSNA and BP, while higher doses (IV, 100 µg; LCV, 10 µg) elevated RSNA and BP. Furthermore, we examined effects of antagonists of histaminergic (H1 and H3) receptors on L-carnosine-induced effects. When peripherally and centrally given, thioperamide, an H3 receptor antagonist, blocked RSNA and BP decreases induced by the lower doses of peripheral L-carnosine, while diphenhydramine, an H1 receptor antagonist, inhibited increases induced by the higher doses of peripheral L-carnosine. Moreover, bilateral lesions of the hypothalamic suprachiasmatic nucleus (SCN) eliminated both effects on RSNA and BP induced by the lower (1 µg) and higher (100 µg) doses of perpheral L-carnosine. These findings suggest that low-dose L-carnosine suppresses and high-dose L-carnosine stimulates RSNA and BP, that the SCN and histaminergic nerve are involved in the activities, and that L-carnosine acts in the brain and possibly other organs.