As part of our studies on the design of agonists of the luteinizing hormone-releasing hormone (LH-RH), we have synthesized the [des-Gly-NH2(10)]-LH-RH N-methylhydrazide (1), the corresponding thiosemicarbazide (2), and the N-formyl- (3) N-acetyl- (4) and N-(trifluoroacetyl)hydrazide (5). Analogue 1 may be regarded as isosteric with [des-Gly-NH2(10)]-LH-RH N-alkylamides which are, in general, potent agonists. Analogues 2-5 may be regarded as isosteric with [aza-Gly-NH2(10)]-OH-RH, which is equipotent with the hormone. The required protected intermediates were prepared by solid-phase synthesis, and the free peptides were prepared from them by deprotection with HF, followed by purification on Sephadex G-25. Bioassay of these analogues with rat hemipituitaries in vitro showed the following values as percentages of the hormonal values for the release of LH and FSH respectively: N-methylhydrazide (1), 17 and 11%; semithiocarbazide (2), 6.5 and 4.6%; N-formylhydrazide (3), 15.3 and 10%; N-acetylhydrazide (4), 1.2 and 0.6%; N-(trifluoroacetyl)hydrazide (5), 1.0 and 0.9%. Thus, these types of isosteric substitutions are inimical to the preservation of the high biological activity of LH-RH.