Certain neuropeptides are known to cause a hypotensive response, thought to be due to mast cell degranulation. The effects of five antagonists of luteinizing hormone-releasing hormone on blood pressure and heart rate were compared in the anesthetized rat. When given intravenously, all five compounds induced hypotensive and bradycardiac effects. The order of potency for these effects was Nal-Arg Antagonist approximately detirelix [( N-Ac-D-Nal(2)1, D-pCl-Phe2,D-Trp3,D-hArg(Et2)6,D-Ala10]LHRH) greater than [N-Ac-D-Nal(2)1, D-pCl-Phe2,D-Pal(3)3,D-hArg(Et2)6,L-hArg (Et2)8,D-Ala10]LHRH (RS-26306) approximately antide greater than [N-Ac-D-Nal(2)1, D-pCl-Phe2,D-Pal(3)3,6, L-hArg(Et2)8,D-Ala10]LHRH (RS-15378) and did not parallel the order of antiovulatory potencies of these compounds. The hypotensive activity of LHRH antagonists, therefore, appeared dissociable from their antiovulatory activity. RS-26306 and RS-15378 appeared to have the greatest therapeutic ratios.