A series of 21 peptides were synthesized and tested in a variety of isolated organs in order to determine their potential as neurokinin-2 (NK-2) antagonists. The peptides have been tested in the three monoreceptor systems, the dog carotid artery (NK-1), the rabbit pulmonary artery (NK-2) and the rat portal vein (NK-3) as well as on other preparations containing NK-2 receptors, such as the rat vas deferens, the hamster urinary bladder, the guinea-pig trachea and the human urinary bladder. Some of the compounds have also been tested on the human isolated bronchus. Three compounds, of which two are linear peptides, Ac.Leu-Asp-Gln-Trp-Phe-Gly.NH2, Thr-Asp-Tyr-D-Trp-Val-D-Trp-D-Trp-Arg.NH2 and a cyclic one, cyclo[Gln-Trp-Phe-Gly-Leu-Met] have been shown to reduce or eliminate the effects of neurokinin A (NKA) in practically all the preparations containing NK-2 receptors. The first compound was found to be selective for the NK-2 receptor and showed only agonistic or no activity on the other receptor systems, while the second compound showed some antagonistic effects not only on the NK-2 but also on the other systems. The cyclic compound was found to be fairly selective for the NK-2 receptor. The first compound (Ac.Leu-Asp-Gln-Trp-Phe-Gly.NH2) was characterized with respect to its specificity for neurokinins (NK): it was found to be inactive on receptors for acetylcholine, noradrenaline, angiotensin and des Arg9-bradykinin in the rabbit pulmonary artery. Moreover, the compound exerted a competitive type of antagonism on the rabbit pulmonary artery and on the hamster urinary bladder. Although of moderate affinity, the NK-2 receptor antagonists described in this paper provide important tools for pharmacological studies on NK.