Responses to a newly synthesized human adrenomedullin (hADM) analog, hADM(16-31), were investigated in the rat and cat. Unlike the full-sequence peptide, which has potent hypotensive activity, hADM(16-31) had pressor activity in the rat but not in the cat. Injection of hADM(16-31) in doses of 10-300 nmol/kg IV induced dose-dependent increases in systemic arterial pressure in the rat, and the peptide was approximately 10-fold less potent than norepinephrine when doses are compared on a nanomole basis. In contrast, injection of hADM(16-31) in doses up to 1000 nmol/kg IV had no significant effect on systemic arterial pressure in the cat. Increases in systemic arterial pressure in response to hADM(16-31) in the rat were significantly reduced after administration of phentolamine or reserpine. These data suggest that increases in systemic arterial pressure in response to hADM(16-31) are mediated by release of catecholamines and activation of α-adrenergic receptors in the rat. These data show that hADM(16-31) has significant pressor activity and that there are marked species differences in the response to hADM(16-31).