The effect of combination of the hydrophilic aza‐Gly substitution (NHNHCO) at position 10 with hydrophobic, unnatural D‐amino acids in position 6 on the potency of luteinizing hormone‐releasing hormone (LH‐RH) analogues has been investigated. Previously the aza‐Gly residue was shown to provide protection from enzymatic cleavage and lead to potency increases in a less hydrophobic series. The compounds were prepared by coupling of the corresponding nona‐peptide acids with semicarbazide hydrochloride by theN,N′‐dicyclohexylcarbodiimide/1‐hydroxybenzotriazole procedure. The required nonapeptide acids were prepared by the solid phase method on chloromethyl‐polystyrene resin using HF/anisole deprotection. The products were purified by preparative reversed‐phase high‐performance liquid chromatography. The analogues were tested in a rat estrous cyclicity suppression assay designed to show the paradoxical antifertility effects of these compounds. The potencies of [6‐(3‐(benz‐imidazol‐2‐yl)‐D‐alanine), 10‐aza‐glycine] LH‐RH and [6‐(3‐(5,6‐dimethylbenzimidazol‐2‐yl)‐D‐alanine), 10‐aza‐glycine]LH‐RH are 40 and 190 times that of LH‐RH respectively. The most active compound in this series is [6‐(3‐(2‐naphthyl)‐D‐alanine), 10‐aza‐glycine] LH‐RH with a potency 230 times that of LH‐RH. This compound is 2.3 times as potent as the standard (