Synthetic human tumor hypercalcemic factor (1-34, hHF) was compared with parathyroid hormone (human sequence, 1-34; hPTH) for vasorelaxant activity in isolated rabbit renal artery segments. The hHF exhibited a potent (IC50 = 1.3 x 10(-9) M) and profound (98%) relaxation which was significantly greater in magnitude than that obtained for hPTH (IC50 = 4.5 x 10(-9) M; maximal relaxation = 78%). The relaxations to both peptides were concentration-dependent and not associated with changes in cyclic AMP levels. These results demonstrate a parathyroid hormone-like response, independent of adenylate cyclase activation, in isolated renal arteries. Renal vasodilation may be important for the effects on renal function shared by these two peptides.