Ever increasing potency is an international goal for antagonists of the luteinizing hormone releasing hormone (LHRH). [N-Ac-D-2-Nal1,D-pClPhe2, D-3-Pal3,Ser4,Arg5,D-3-Pal6,Leu7,Arg8,Pro9,D- Ala10]-NH2 caused 60%/125 ng inhibition of ovulation in the rat, and appears to be the most potent antagonist yet described. Strategy of design was the replacement of D-Arg6 with D-3-Pal6 and of Tyr5 with Arg5. Replacing Arg5 with His5 reduced activity by 50% at 250 ng. Both the Arg5 and His5 analogs showed 100% inhibition of ovulation at 0.5 microgram. Of ten pairs of analogs with D-3-Pal6 and D-Arg6, 3/10 with D-3-Pal6 were more potent than those with D-Arg6. Histamine release was less for the D-3-Pal6 peptides of three pairs.